This article is part of the special JITC series: SITC 40th Anniversary: I-O Progress and Potential

This article is part of the special JITC series: SITC 40th Anniversary: I-O Progress and Potential

This article is part of the special JITC series: The Next Wave of Immuno-oncology: A Roadmap from the Society for Immunotherapy of Cancer (SITC)

Notice: The name of author Lian Liu was incorrectly spelled as Lian Lu.

SITC continuously evaluates the field for emerging data and new FDA approvals. Updates to the recommendations, tables, treatment algorithms, and/or guideline text in this publication are made with the approval of the SITC Lung Cancer and Mesothelioma CPG Expert Panel. More information on the SITC Guidelines can be found at sitcancer.org/guidelines. Last updated May 2025.

Addendum Summary

The SITC Lung Cancer and Mesothelioma CPG includes an addendum incorporating updates to the treatment landscape made by the SITC Lung Cancer and Mesothelioma CPG Expert Panel. A detailed description of the addendum updates can be found here: https://jitc.bmj.com/content/13/7/e003956add1

Last reviewed 02/10/2025 (v1.4 Update)

SITC continuously evaluates the field for emerging data and new FDA approvals. Updates to the recommendations, tables, treatment algorithms, and/or guideline text in this publication are made with the approval of the SITC Lymphoma Cancer Immunotherapy Guideline Expert Panel. More information on the SITC Guidelines can be found at sitcancer.org/guidelines.

v1.4 Update Summary

• The FDA granted approval of denileukin diftitox-cxdl for the treatment of patients with stage 1 to 3 relapsed/refractory cutaneous TCL after at least 1 prior systemic therapy in August 2024 [Ref 242-243].

• The FDA granted accelerated approval of epcoritamab for adult patients with relapsed or refractory FL after two or more lines of systemic therapy in June 2024 [Ref 244, 245].

• The FDA granted approval of lisocabtagene maraleucel for adult patients with relapsed or refractory mantle cell lymphoma MCL who have received at least two prior lines of systemic therapy, including a Bruton tyrosine kinase inhibitor (BTKi) in May 2024 [Ref 246].

• The FDA granted accelerated approval of lisocabtagene maraleucel for adults with relapsed or refractory FL who have received two or more prior lines of systemic therapy in May 2024 [Ref 246].

• The FDA granted accelerated approval of lisocabtagene maraleucel for adult patients with relapsed or refractory CLL or SLL who have received at least 2 prior lines of therapy, including a BTKi and a B-cell lymphoma 2 (BCL-2) inhibitor in March 2024 [Ref 246].

• The FDA granted accelerated approval of zanubrutinib with obinutuzumab for relapsed or refractory FL after two or more lines of systemic therapy in March 2024 [Ref 247, 248].

• The FDA granted accelerated approval of glofitamab for relapsed or refractory diffuse large B-cell lymphoma DLBCL, not otherwise specified (NOS) or LBCL arising from FL, after two or more lines of systemic therapy in June 2023 [Ref 249].

• The FDA granted accelerated approval of epcoritamab for relapsed or refractory DLBCL NOS, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma (HGBL) after two or more lines of systemic therapy in May 2023 [Ref 244].

• The FDA granted approval of polatuzumab vedotin with a rituximab product, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for adult patients who have previously untreated DLBCL, NOS or HGBL and who have an International Prognostic Index (IPI) score of 2 or greater in April 2023 [Ref 250, 251].

• The FDA granted accelerated approval of mosunetuzumab for adult patients with relapsed or refractory FL after two or more lines of systemic therapy in December 2022 [Ref 252].

• Data have been reported on the safety and efficacy of lenalidomide + obinutuzumab for relapsed or refractory FL and marginal zone lymphoma [Ref 253, 254].

• Data have been reported on the safety and efficacy of nivolumab + AVD for patients with Hodgkin lymphoma [Ref 255].

• Data have been reported on the safety and efficacy of nivolumab + chemotherapy and pembrolizumab + chemotherapy for patients with relapsed or refractory Hodgkin lymphoma [Ref 256–258].

• Data have been reported on the safety and efficacy of BV-nivolumab for the treatment of R/R PMBCL [Ref 259].

v1.3 Update Summary

• The FDA granted approval of lisocabtagene maraleucel for the treatment of adult patients with LBCL who have refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; or refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age in June 2022 [Ref 246].

• The FDA granted accelerated approval of tisagenlecleucel for the treatment of adult patients with relapsed or refractory FL following 2 or more lines of systemic therapy in May 2022 [Ref 113].

• The FDA granted approval of axicabtagene ciloleucel for adult patients with LBCL that is refractory to first-line chemoimmunotherapy or relapses within 12 months of first-line chemoimmunotherapy in April 2022 [Ref 111].

• The FDA granted accelerated approval of axicabtagene ciloleucel for adult patients with relapsed or refractory FL after two or more lines of systemic therapy in March 2021 [Ref 111].

v1.2 Update Summary

• The FDA granted accelerated approval of loncastuximab tesirine-lpyl for the treatment of adult patients with relapsed or refractory LBCL after two or more lines of systemic therapy, including DLBCL NOS, DLBCL arising from low grade lymphoma, and HGBL in April 2021 [Ref 260].**

v1.1 Update Summary

• The FDA granted approval of lisocabtagene maraleucel for the treatment of R/R large B-cell lymphoma after two or more lines of systemic therapy, including DLBCL not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, PMBL, and FL grade 3B in February 2021. [Ref 246, 261]

Last Reviewed 3/15/2024 (v1.2 Update)

SITC continuously evaluates the field for practice-changing data and new FDA approvals. The information on this page provides a detailed overview of updates to the guideline content based on changes in the field. Updates to the guideline outlined below were made with the approval of SITC's Breast Cancer CPG Expert Panel. More information on SITC Guidelines can be found at sitcancer.org/guidelines.

v1.2 Update Summary

• The FDA granted accelerated approval for dostarlimab for the treatment of dMMR recurrent or advanced solid tumors (along with the VENTANA MMR RxDx Panel companion diagnostic to detect dMMR) that have progressed on or following prior treatment and who have no satisfactory alternative treatment options on August 17, 2021. Based on these approvals, the Breast Cancer CPG has been updated in the following locations: Immunotherapy with PD-(L)1 Inhibitors for the Treatment of Advanced/Metastatic Breast Cancer and Diagnostics and Biomarker Testing in Patients with Advanced/Metastatic Breast Cancer. [Ref 290]

• The FoundationOne CDx assay was approved as the companion diagnostic for identifying patients with MSI-H tumors for treatment with pembrolizumab in February 2022. Based on this approval, the Breast Cancer CPG has been updated in the following locations: Diagnostics and Biomarker Testing in Patients with Advanced/Metastatic Breast Cancer. [Ref 291]

See highlighted text for updated content and more detailed information.

v1.1 Update

Revised recommendation:

• For patients with treatment-refractory, immunotherapy-naïve, advanced MSS/pMMR BTC, treatment with a clinical trial is preferred but the following are considered suitable if a trial is not available: a) lenvatinib plus pembrolizumab (LE:3) or nivolumab (LE:3), b) nivolumab plus ipilimumab (LE:3), or c) nivolumab (LE:3) or pembrolizumab (LE:3).

Update 8-17-22

Upon survey of the Expert Panel following the FDA approvals for use of first-line pembrolizumab plus lenvatinib or nivolumab plus cabozantinib for aRCC, this text was modified as follows:

For first-line VEGF TKI + checkpoint inhibitor combination therapy for RCC, the Expert Panel recommends the following: cabozantinib plus nivolumab (40%), lenvatinib plus pembrolizumab (33%), axitinib plus pembrolizumab (20%), and not applicable – would never choose a VEGF TKI plus checkpoint inhibitor combination for this population (7%).

This article is part of the special JITC series: The Next Wave of Immuno-oncology: A Roadmap from the Society for Immunotherapy of Cancer (SITC)

Last Reviewed 5/25/24 (v1.1 Update)

SITC continuously evaluates the field for practice-changing data and new FDA approvals. The information on this page provides a detailed overview of updates to the guideline content based on changes in the field. Updates to the guideline outlined below were made with the approval of SITC's Gynecology Cancer CPG Expert Panel. More information on SITC Guidelines can be found at sitcancer.org/guidelines.

v1.1 Update Summary

• The FDA granted approval of pembrolizumab with chemoradiotherapy FIGO 2014 Stage III-IVA cervical cancer on January 12, 2024. Based on this approval, the Gynecologic Cancer CPG has been updated in the following location: Immunotherapy for the treatment of cervical cancer - Recommended immunotherapy treatments for cervical cancer (including Table 2). [Ref 13, 299, 300]

• The FDA granted approval of dostarlimab with carboplatin and paclitaxel, followed by single-agent dostarlimab for dMMR or MSI-H (as determined by an FDA-approved test) primary advanced or recurrent endometrial cancer on July 31, 2023. Based on this approval, the Gynecologic Cancer CPG has been updated in the following location: Immunotherapy for the treatment of endometrial cancer - Recommended immunotherapy treatments for endometrial cancer (including Table 3). [Ref 15, 121, 301]

See highlighted text for updated content and more detailed information.

v1.1 Update

The following references have been added:

1. Food and Drug Administration, BeiGene. TEVIMBRA (tislelizumab) prescribing information. Available: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=761380 Accessed 5/12/25

2. Food and Drug Administration, Astellas. VYLOY (zolbetuximab-clzb) prescribing information. Available: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=761365 Accessed 5/8/25

3. Food and Drug Administration, Merck & Co. KEYTRUDA (pembrolizumab) prescribing information. Available: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125514 Accessed 1/8/25

4. Liu L, Woo Y, D’Apuzzo M, Melstrom L, Raoof M, Liang Y, et al. Immunotherapy-Based Neoadjuvant Treatment of Advanced Microsatellite Instability–High Gastric Cancer: A Case Series. Journal of the National Comprehensive Cancer Network. 2022;20(8):857-65.

5. Kelly RJ, Lee J, Bang Y-J, Almhanna K, Blum-Murphy M, Catenacci DV, et al. Safety and efficacy of durvalumab and tremelimumab alone or in combination in patients with advanced gastric and gastroesophageal junction adenocarcinoma. Clinical Cancer Research. 2020;26(4):846-54.

6. Moehler M, Oh DY, Kato K, Arkenau T, Tabernero J, Lee KW, Rha SY, Hirano H, Spigel D, Yamaguchi K, Wyrwicz L. First-Line Tislelizumab Plus Chemotherapy for Advanced Gastric Cancer with Programmed Death-Ligand 1 Expression≥ 1%: A Retrospective Analysis of RATIONALE-305. Advances in Therapy. 2025 Mar 13:1-21.

7. Shitara K, Lordick F, Bang YJ, Enzinger P, Ilson D, Shah MA, Van Cutsem E, Xu RH, Aprile G, Xu J, Chao J. Zolbetuximab plus mFOLFOX6 in patients with CLDN18. 2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. The Lancet. 2023 May 20;401(10389):1655-68.

8. Rha SY, Oh D-Y, Yañez P, Bai Y, Ryu M-H, Lee J, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial. The Lancet Oncology. 2023;24(11):1181-95.

9. Shen L, Kato K, Kim S-B, Ajani JA, Zhao K, He Z, et al. Tislelizumab versus chemotherapy as second-line treatment for advanced or metastatic esophageal squamous cell carcinoma (RATIONALE-302): a randomized phase III study. Journal of clinical oncology. 2022;40(26):3065-76

10. Janjigian YY, Kawazoe A, Bai Y, Xu J, Lonardi S, Metges JP, et al. Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial. The Lancet. 2023;402(10418):2197-208

11. European Medicines Agency. KEYTRUDA (pembrolizumab) product information . Available: https://www.ema.europa.eu/en/medicines/human/EPAR/keytruda#authorisation-details Accessed 1/8/25

12. Kelley RK, Ueno M, Yoo C, Finn RS, Furuse J, Ren Z, et al. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet. 2023;401(10391):1853-65

13. Andre T, Elez E, Van Cutsem E, Jensen LH, Bennouna J, Mendez G, Schenker M, de la Fouchardiere C, Limon ML, Yoshino T, Li J. Nivolumab plus Ipilimumab in Microsatellite-Instability–High Metastatic Colorectal Cancer. New England Journal of Medicine. 2024 Nov 28;391(21):2014-26.

14. Food and Drug Administration, Bristol Myers Squibb Company. OPDIVO (nivolumab) prescribing information. Available: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125554 Accessed 5/14/25

15. Food and Drug Administration, Bristol Myers Squibb Company. YERVOY (ipilimumab) prescribing information. Available: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125377 Accessed 5/14/25

Last reviewed 5/28/2025 (v1.1 Update)

SITC continuously evaluates the field for emerging data and new FDA approvals. Updates to the recommendations, tables, treatment algorithms, and/or guideline text in this publication are made with the approval of the SITC Gastrointestinal Cancer CPG Expert Panel. More information on SITC Guidelines can be found at sitcancer.org/guidelines.

v1.1 Update Summary

• The FDA approved nivolumab in combination with ipilimumab for adult and pediatric patients 12 years of age and older with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC) in April 2025 [Ref 242, Ref 243].

• The FDA approved tislelizumab in combination with platinum and fluoropyrimidine-based chemotherapy for the first-line treatment of adult patients with unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 (≥1) in December 2024 [Ref 229].

• The FDA approved zolbetuximab-clab in combination with platinum and fluoropyrimidine-containing chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test in October 2024 [Ref 230].

• The FDA approved tislelizumab for the treatment of adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) after prior systemic chemotherapy that did not include a PD-L1 inhibitor in March 2024 [Ref 229].

• The indication of pembrolizumab with trastuzumab, fluoropyrimidine, and platinum-containing chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma was restricted to patients with CPS greater than or equal to 1, as determined by an FDA-approved test, in November 2023 [Ref 231].

• The FDA approved pembrolizumab with fluoropyrimidine- and platinum-containing chemotherapy as first-line treatment for adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma in November 2023 [Ref 231].

• The FDA approved pembrolizumab with gemcitabine and cisplatin for the treatment of locally advanced unresectable or metastatic biliary tract cancer (BTC) in October 2023 [Ref 231].

• Additional changes made to address practice-changing data and updates in the field.

See the highlighted text for updated content and more detailed information.

v1.1 Update

Since guideline publication, additional neoadjuvant/pre-operative studies have shown efficacy with ICIs for patients with dMMR/MSI-H gastric/GEJ adenocarcinoma. These regimens are not yet FDA-approved [Ref 96, 97, 160, 232, 233].

v1.1 Update

Since guideline publication, the approval for pembrolizumab with trastuzumab, fluoropyrimidine, and platinum-containing chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma was restricted to patients with CPS greater than or equal to 1, as determined by an FDA-approved test [Ref 231].

v1.1 Update

Revised recommendation:

• For patients with MSI-H/dMMR resectable rectal cancer, phase II data from a single-center study of neoadjuvant ICI therapy suggest remarkable activity (LE:3). ICI as neoadjuvant or definitive therapy with non-operative management in consultation with a multidisciplinary team can be considered, but clinical trial participation is preferred.

v1.1 Update

Revised recommendation:

• For patients with untreated, metastatic, MSI-H/dMMR CRC, pembrolizumab monotherapy (LE:2) or nivolumab plus ipilimumab (LE:2) are treatment options.

v1.1 Update

Since guideline publication, the FDA approved nivolumab in combination with ipilimumab for adult and pediatric patients 12 years of age and older with unresectable or metastatic MSI-H or dMMR CRC in April 2025. Approval was based on results of the CheckMate 8HW and a primary endpoint of PFS. At a median follow-up of 31.5 months, the 24-month PFS for patients who received nivolumab plus ipilimumab was 72% (95% CI 64% to 79%) compared to 14% (95% CI 6% to 25%) for patients who received chemotherapy [Ref 241, 242, 243].

Figure 2 - Advanced CRC testing and treatment algorithm has been updated to include FDA approvals and practice changing data since guideline publication. See here for revised Figure 2.

v1.1 Update

Revised recommendation:

• For patients with treatment-refractory, immunotherapy-naïve, advanced MSS/pMMR BTC, treatment with a clinical trial is preferred but the following are considered suitable if a trial is not available: a) lenvatinib plus pembrolizumab (LE:3) or nivolumab (LE:3), b) nivolumab plus ipilimumab (LE:3), or c) nivolumab (LE:3) or pembrolizumab (LE:3).

v1.1 Update

Revised recommendation:

• For patients with untreated, advanced BTC, treatment with combination gemcitabine and cisplatin with durvalumab (LE:2) or pembrolizumab (LE:2) is recommended unless a contraindication to immunotherapy exists.

v1.1 Update

Since guideline publication, pembrolizumab with gemcitabine and cisplatin for the treatment of locally advanced unresectable or metastatic BTC was FDA-approved in October 2023. Approval was based on data from the phase III KEYNOTE-966 trial (NCT04003636), which randomized (1:1) 1,069 patients with unresectable or metastatic BTC who had not received prior systemic therapy for advanced disease to receive either pembrolizumab (n=533) or placebo (n=536), combined with gemcitabine and cisplatin. The primary outcome was OS. At a median follow-up of 25.6 months, the median OS was 12.7 months (95% CI 11.5 to 13.6) in the pembrolizumab group and 10.9 months (95% CI 9.9 to 11.6) in the placebo group (HR 0.83; 95% CI 0.72 to 0.95; one-sided p=0.0034). Potentially immune-mediated adverse events and infusion reactions occurred in 22% of patients in the pembrolizumab group and 4% of patients in the placebo group. Overall treatment-related grade 3-4 AEs occurred in 70% of patients in the pembrolizumab group and 69% of patients in the placebo group [Ref 240].

v1.1 Update

Since guideline publication, the FDA approved pembrolizumab with gemcitabine and cisplatin for the treatment of locally advanced unresectable or metastatic BTC in October 2023 [Refs 231, 240].

v1.1 Update

Since guideline publication, the FDA approved tislelizumab for the treatment of adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) after prior systemic chemotherapy that did not include a PD-L1 inhibitor in March 2024 [Refs 229, 237].

v1.1 Update

New Panel recommendations:

• For patients with unresectable or metastatic ESCC following prior systemic chemotherapy that did not include a PD-1/PD-L1 inhibitor, tislelizumab is recommended (LE:2).

• For patients with untreated, locally advanced unresectable or metastatic, HER2-negative, PD-L1 ≥1 gastric or GEJ adenocarcinoma, nivolumab, pembrolizumab, or tislelizumab with fluoropyrimidine- and platinum-containing chemotherapy is recommended (LE:2). For patients with locally advanced unresectable or metastatic HER2-negative, CLDN18.2-positive gastric or GEJ adenocarcinoma, zolbetuximab in combination with fluoropyrimidine- and platinum-containing chemotherapy is recommended (LE:2). There are no comparative data regarding the efficacy of zolbetuximab plus chemotherapy versus an ICI plus chemotherapy where both zolbetuximab and ICI therapy are indicated.

v1.1 Update

Since guideline publication, additional data have shown efficacy with ICIs for pre-operative use in patients with dMMR/MSI-H gastric/GEJ adenocarcinoma [Ref 96, 97, 160, 232, 233].

v1.1 Update

Revised recommendation:

• For patients with untreated, PD-L1 CPS ≥1, HER2-positive, advanced esophagogastric adenocarcinoma, chemotherapy plus trastuzumab plus pembrolizumab is recommended (LE:2).

v1.1 Update

In addition to the FDA-approved regimens for ESCC described in this section, single-agent tislelizumab received FDA approval for the treatment of adult patients with unresectable or metastatic ESCC following prior systemic chemotherapy that didn't include a PD-1/PD-L1 inhibitor in March 2024. Approval was based on significant improvement to OS for patients receiving tislelizumab over those receiving chemotherapy in the randomized, phase 3 RATIONALE-302 trial (NCT03430843). Survival benefit of tislelizumab treatment was consistent across all predefined sub-groups, including baseline PD-L1 expression status. See here for revised Table 3 - Landmark trials leading to FDA approvals for ICIs used to treat unresectable/metastatic, previously treated esophagogastric cancers v1.1 [Ref 237].

v1.1 Update

Since guideline publication, pembrolizumab with trastuzumab, fluoropyrimidine and platinum-containing chemotherapy was approved by the European Medicines Agency for the first-line treatment of locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma in adults whose tumors express PD-L1 with a CPS greater than or equal to 1 [Ref 239].

v1.1 Update

Since guideline publication, the indication of pembrolizumab with trastuzumab, fluoropyrimidine, and platinum-containing chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma was restricted to patients with CPS greater than or equal to 1, as determined by an FDA-approved test in November 2023. This was based on a prespecified interim analysis of the fully enrolled KEYNOTE-811 trial (NCT03615326) (n=698) where sub-group analysis of patients stratified by PD-L1 expression showed no benefit of pembrolizumab addition in patients with CPS < 1. See here for revised Table 2 - Landmark trials leading to FDA approvals for ICIs used to treat unresectable/metastatic, treatment-naïve esophagogastric cancers v1.1 [Ref 231, 238].

v1.1 Update

Table 3 - Landmark trials leading to FDA approvals for ICIs used to treat unresectable/metastatic, previously treated esophagogastric cancers has been updated to include data from the RATIONALE-302 trial to reflect a new approval. See here for revised Table 3 [Ref 229, 237].

v1.1 Update

Table 2 - Landmark trials leading to FDA approvals for ICIs used to treat unresectable/metastatic, treatment-naïve esophagogastric cancers has been updated to include data from the KEYNOTE-859 and RATIONALE-305 trials to reflect new approvals. See here for revised Table 2 [Ref 229, 231, 234, 236].

v1.1 Update

Since guideline publication, the FDA approved pembrolizumab with fluoropyrimidine- and platinum-containing chemotherapy for the treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma in November 2023 [Ref 231].

v1.1 Update

Figure 1 - Advanced esophagogastric diagnostic testing and treatment algorithm has been updated to include new FDA approvals and indication changes since guideline publication. See here for revised Figure 1A and Figure 1B [Ref 229, 230, 231].

v1.1 Update

Since guideline publication, zolbetuximab and six indications for immune checkpoint inhibitors are now approved by the FDA for the first-line treatment of advanced, esophagogastric cancers [Ref 229, 230, 231].

v1.1 Update

Since guideline publication, the FDA approved tislelizumab in combination with platinum and fluoropyrimidine-based chemotherapy for the first-line treatment of adult patients with unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 (≥1) in December 2024. This approval was based on data from the randomized double-blind RATIONALE-305 trial (NCT03777657). Patients who received tislelizumab in combination with chemotherapy experienced an improved OS compared to those who received placebo plus chemotherapy, primarily in patients with PD-L1 expression ≥1. See here for revised Table 2 - Landmark trials leading to FDA approvals for ICIs used to treat unresectable/metastatic, treatment-naïve esophagogastric cancers v1.1 [Ref 229, 234].

Since guideline publication, the FDA approved zolbetuximab-clab in combination with platinum and fluoropyrimidine-containing chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma whose tumors are CLDN18.2-positive as determined by an FDA-approved test in October 2024. This approval was based on an improved OS and PFS in the phase III double-blind SPOTLIGHT trial (NCT03504397) which randomly assigned patients with CLDN18.2-positive, HER2-negative gastric or gastroesophageal junction adenocarcinoma to receive either zolbetuximab plus mFOLFOX6 (n=283) or placebo plus mFOLFOX6 (n=282). Compared to patients who received placebo plus chemotherapy, patients who received zolbetuximab plus chemotherapy experienced an improved median PFS (10.6 vs 8.7 mo; HR 0.75 [95% CI 0.60 to 0.94]; p = 0.0066), and an improved median OS (18.2 vs 15.5 mo; HR 0.75 [95% CI 0.60 to 0.94]; p = 0.0052) [Ref 230, 235].

v1.1 Update

New Panel recommendation:

• For patients with resectable gastric/GEJ adenocarcinoma that is dMMR/MSI-H, pre-operative ICIs should be considered in consultation with a multidisciplinary team (LE:2).

v1.1 Update

New Panel recommendation:

• For patients with gastric or GEJ adenocarcinoma, CLDN 18.2 testing should be performed using a validated antibody (LE:2).

v1.1 Update

Revised recommendation:

• For all patients with a GI cancer, MSI/MMR status and TMB testing (for MSS/pMMR tumors) should be performed on tumor tissue in a CLIA-certified lab (LE:3). MSI status and TMB may be obtained by NGS. MSI can also be determined by PCR. MMR status may be obtained by IHC.

This article is part of the special JITC series: SITC 40th Anniversary: I-O Progress and Potential

This article is part of the special JITC series: SITC 40th Anniversary: I-O Progress and Potential

This article is part of the special JITC series: SITC 40th Anniversary: I-O Progress and Potential

This article is part of the special JITC series: SITC 40th Anniversary: I-O Progress and Potential

This article is part of the special JITC series: SITC 40th Anniversary: I-O Progress and Potential

This article is part of the special JITC series: SITC 40th Anniversary: I-O Progress and Potential

This article is part of the special JITC series: SITC 40th Anniversary: I-O Progress and Potential

This article is part of the special JITC series: The Next Wave of Immuno-oncology: A Roadmap from the Society for Immunotherapy of Cancer (SITC)

This article is part of the special JITC series: The Next Wave of Immuno-oncology: A Roadmap from the Society for Immunotherapy of Cancer (SITC)

v1.4 Update

The following references have been added:

1. Food and Drug Administration, Citus Pharmaceuticals. LYMPHIR (denileukin diftitox-cxdl) prescribing information. Available: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=761312 Accessed 1/10/25

2. Foss FM, Kim YH, Prince H, Kuzel TM, Yannakou CK, Ooi CE, Xing D, Sauter N, Singh P, Czuczman M, Duvic M. Efficacy and safety of E7777 (improved purity Denileukin diftitox [ONTAK]) in patients with relapsed or refractory cutaneous T-cell lymphoma: results from pivotal study 302. Blood. 2022 Nov 15;140(Supplement 1):1491-2.

3. Food and Drug Administration, Genmab. EPKINLY (epcoritamab) prescribing information. Available: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process Accessed 1/10/25

4. Linton KM, Vitolo U, Jurczak W, Lugtenburg PJ, Gyan E, Sureda A, Christensen JH, Hess B, Tilly H, Cordoba R, Lewis DJ. Epcoritamab monotherapy in patients with relapsed or refractory follicular lymphoma (EPCORE NHL-1): a phase 2 cohort of a single-arm, multicentre study. The Lancet Haematology. 2024 Jun 15.

5. Food and Drug Administration, Juno Therapeutics. BREYANZI (lisocabtagene maraleucel) prescribing information. Available: https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/breyanzi-lisocabtagene-maraleucel Accessed 1/10/25

6. Food and Drug Administration, Genentech. GAZYVA (obinutuzumab) prescribing information. Available: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125486s034lbl.pdf

7. Zinzani PL, Mayer J, Flowers CR, Bijou F, De Oliveira AC, Song Y, Zhang Q, Merli M, Bouabdallah K, Ganly P, Zhang H. ROSEWOOD: a phase II randomized study of zanubrutinib plus obinutuzumab versus obinutuzumab monotherapy in patients with relapsed or refractory follicular lymphoma. Journal of Clinical Oncology. 2023 Nov 20;41(33):5107-17.

8. Food and Drug Administration, Genentech. COLUMVI (glofitamab) prescribing information. Available: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process Accessed 1/10/25

9. Food and Drug Administration, Genentech. POLIVY (polatuzumab vedotin) prescribing information. Available: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process Accessed 1/10/25

10. Tilly H, Morschhauser F, Sehn LH, Friedberg JW, Trněný M, Sharman JP, Herbaux C, Burke JM, Matasar M, Rai S, Izutsu K. Polatuzumab vedotin in previously untreated diffuse large B-cell lymphoma. New England Journal of Medicine. 2022 Jan 27;386(4):351-63.

11. Food and Drug Administration, Genentech. LUNSUMIO (mosunetuzumab) prescribing information. Available: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process Accessed 1/10/25

12. Morschhauser F, Le Gouill S, Feugier P, Bailly S, Nicolas-Virelizier E, Bijou F, et al. Obinutuzumab combined with lenalidomide for relapsed or refractory follicular B-cell lymphoma (GALEN): a multicentre, single-arm, phase 2 study. The Lancet Haematology. 2019;6(8):e429-e37.

13. Gurumurthi A, Chin CK, Feng L, Fowler NH, Strati P, Hagemeister FB, Fayad LE, Westin JR, Obi C, Arafat J, Nair R. Safety and activity of lenalidomide in combination with obinutuzumab in patients with relapsed indolent non-Hodgkin lymphoma: a single group, open-label, phase 1/2 trial. EClinicalMedicine. 2024 Aug 1;74.

14. Herrera AF, LeBlanc M, Castellino SM, Li H, Rutherford SC, Evens AM, et al. Nivolumab+ AVD in advanced-stage classic Hodgkin’s lymphoma. New England Journal of Medicine. 2024;391(15):1379-89.

15. Moskowitz AJ, Shah G, Schöder H, Ganesan N, Drill E, Hancock H, et al. Phase II trial of pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin as second-line therapy for relapsed or refractory classical Hodgkin lymphoma. Journal of Clinical Oncology. 2021;39(28):3109-17.

16. Mei MG, Lee HJ, Palmer JM, Chen R, Tsai N-C, Chen L, et al. Response-adapted anti-PD-1–based salvage therapy for Hodgkin lymphoma with nivolumab alone or in combination with ICE. Blood, The Journal of the American Society of Hematology. 2022;139(25):3605-16.

17. Bryan LJ, Casulo C, Allen PB, Smith SE, Savas H, Dillehay GL, et al. Pembrolizumab added to ifosfamide, carboplatin, and etoposide chemotherapy for relapsed or refractory classic Hodgkin lymphoma: a multi-institutional phase 2 investigator-initiated nonrandomized clinical trial. JAMA oncology. 2023;9(5):683-91.

18. Zinzani PL, Santoro A, Gritti G, Brice P, Barr PM, Kuruvilla J, Cunningham D, Kline J, Johnson NA, Mehta-Shah N, Lisano J. Nivolumab combined with brentuximab vedotin for R/R primary mediastinal large B-cell lymphoma: a 3-year follow-up. Blood Advances. 2023 Sep 26;7(18):5272-80.

19. Food and Drug Administration, ADC Therapeutics. ZYNLONTA (loncastuximab tesirine) prescribing information. Available: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process Accessed 1/10/25

20. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study https://pubmed.ncbi.nlm.nih.gov/32888407

v1.4 Update

Revised Recommendation:

• For the second-line treatment of cHL, there was consensus that patients should receive salvage chemotherapy or immunotherapy, and should receive autoSCT, if eligible. Treatment options for pre-autoSCT chemotherapy or immunotherapy include BV+bendamustine, ICE, BV+nivolumab, BV monotherapy, or chemotherapy + nivolumab or pembrolizumab. The panel noted that BV is FDA-approved for consolidation treatment following autoSCT, but that the trial supporting this data only examined patients who were BV-naïve, and that BV consolidation in patients who have previously received BV is still investigational.

v1.4 Update

In addition to the approved immunotherapies described in this section, since guideline publication the following approvals and practice-changing data have been reported:

Diffuse large B cell lymphoma

Epcoritamab received an accelerated approval for relapsed or refractory DLBCL NOS, including DLBCL arising from indolent lymphoma, and HGBL after two or more lines of systemic therapy in May 2023. Approval was based on the primary endpoint ORR from EPCORE NHL-1 (NCT03625037), a single-arm phase I/II trial. The ORR for epcoritamab (n=148) was 61% (95% CI 52.5% to 68.7%), with a 9-month DOR rate of 63% (95% CI 51.5% to 72.4%). Any grade CRS occurred in 41% of patients (2.5% were grade 3), and ICANS occurred in less than 10% of patients treated with epcoritamab. [Ref 244].

Glofitamab received an accelerated approval for relapsed or refractory DLBCL, NOS or LBCL arising from FL, after two or more lines of systemic therapy in June 2023. Approval was based on the primary endpoints of ORR and DOR from NP30179 (NCT03075696), a single-arm phase I/II trial. The ORR for glofitamab (n=132) was 56% (95% CI 47% to 65%), and the median DOR was 18.4 months (95% CI 11.4 to NE). Any-grade CRS occurred in 70% of patients (4.1% were grade 3 or higher), and any-grade ICANS occurred in 4.8% of patients. [Ref 249].

Polatuzumab vedotin with a rituximab product, cyclophosphamide, doxorubicin, and prednisone ([pola-]R-CHP) was approved for adult patients who have previously untreated DLBCL, NOS or HGBL and who have an IPI score of 2 or greater in April 2023. Approval was based on the primary endpoint of PFS from POLARIX (NCT03274492), a randomized phase III trial assessing pola-R-CHP (n=440) compared to R-CHOP (n=439). PFS in the pola-R-CHP group was significantly improved (HR 0.73; 95% CI 0.57 to 0.95; p=0.0177). Serious AEs occurred in 34% of patients who received pola-R-CHP and 30.6% of patients who received R-CHOP [Ref 250, 251].

Mantle cell lymphoma

Lisocabtagene maraleucel was approved for adult patients with relapsed or refractory MCL who have received at least two prior lines of systemic therapy, including a BTKi in May 2024. Approval was based on the primary endpoint of ORR from TRANSCEND-MCL (NCT02631044), a single-arm phase I trial that assessed treatment with lisocabtagene maraleucel (n=68). The ORR was 85.3% (95% CI 74.6% to 92.7%). At a median follow-up of 22.2 months (95% CI 16.7 to 22.8), the median DOR was 13.3 months (95% CI 6.0 to 23.3). Serious AEs occurred in 53% of patients, and any-grade CRS occurred in 61% of patients (1.1% grade 4 or higher). [Ref 261].

Follicular lymphoma

Epcoritamab received an accelerated approval for adult patients with relapsed or refractory FL after two or more lines of systemic therapy in June 2024. Approval was based on the primary endpoints ORR and DOR data from EPCORE NHL-1 (Study GCT3013-01; NCT03625037), a single-arm phase II trial. The ORR for epcoritamab (n=127) was 82% (95% CI 74.1% to 88.2%), and the estimated 12-month DOR rate was 68.4% (95% CI 57.6% to 77.0%). ICANS occurred in 6.0% of patients, and serious infections occurred in 40% of patients. Grade 1–2 CRS events occurred in 49% of patients who received the 3-step dosage [Ref 244, 245].

Lisocabtagene maraleucel received an accelerated approval for adults with relapsed or refractory FL who have received two or more prior lines of systemic therapy in May 2024. Approval was based on the primary endpoint of ORR from TRANSCEND-FL (NCT04245839), a single-arm phase I/II trial. The ORR for lisocabtagene maraleucel (n=94) was 95.7% (95% CI 89%.5 to 98.8%), with a 12-month DOR rate of 80.9% (95% CI 71.0% to 87.7%). Serious AEs occurred in 26% of patients, and any-grade CRS occurred in 59% of patients (0.9% grade 3 or higher). [Ref 246].

Zanubrutinib with obinutuzumab received an accelerated approval for relapsed or refractory FL after two or more lines of systemic therapy in March 2024. Approval was based on the primary endpoints ORR and DOR from Study BGB-3111-212 (ROSEWOOD; NCT03332017), a randomized phase II trial. The ORR in patients treated with zanubrutinib with obinutuzumab (n=145) was 69% (95% CI 61% to 76%) versus 46% (95% CI 34% to 58%) in patients treated with obinutuzumab alone (n=72). The median DOR was NE (95% CI 25.3 to NE) versus 14.0 months (95% CI 9.2 to 25.1), respectively. Serious AEs occurred in 35% of patients with FL who received zanubrutinib with obinutuzumab [Ref 247, 248].

Mosunetuzumab received an accelerated approval for adult patients with relapsed or refractory FL after two or more lines of systemic therapy in December 2022. Approval was based on the primary endpoint of ORR from GO29781 (NCT02500407), a single-arm phase I/II trial. The ORR for mosunetuzumab (n=90) was 80% (95% CI 70% to 88%). Serious AEs occurred in 47% of patients, and grade 2 CRS occurred in 15% of patients, grade 3 in 2%, and grade 4 in 0.5%. [Ref 252].

Follicular lymphoma

Although not FDA-approved, data on lenalidomide + obinutuzumab for relapsed or refractory FL have been reported in the single-arm phase I/II GALEN trial (NCT01582776). The overall response was 79% (95% CI 69% to 87%) for the combination (n=86). Serious AEs were reported in 34% of patients [Ref 251]. Lenalidomide plus obinutuzumab was also assessed in the NCT01995669 trial, which included patients with indolent non-Hodgkin lymphoma (n=60; n=4 with MZL). [Ref 253, 254]

Primary mediastinal large B cell lymphoma

Although not FDA-approved, data on BV-nivolumab for the treatment of R/R PMBCL have been reported in the phase I/II singe-arm CheckMate 436 (NCT02581631) trial. At median follow up of 39.6 months, the ORR for BV-nivolumab (n=30) was 73.3% (95% CI 54.1% to 87.7%), median PFS was 26.0 months (95% CI 2.6 to NR), and median OS was NR. The most frequently occurring grade 3-4 treatment-related AE was neutropenia (53.3%). [Ref 259]

Cutaneous T cell lymphoma

Denileukin diftitox-cxdl was approved for the treatment of patients with stage 1 to 3 relapsed/refractory CTCL after at least 1 prior systemic therapy in August 2024. Approval was based on the primary endpoint of ORR from Study 302 (NCT01871727), a single-arm phase III trial. The ORR for denileukin diftitox-cxdl (n = 69) was 36.2% (95% CI 25.0% to 48.7%). Serious AEs occurred in 38% of patients. [Ref 242, 243]

v1.3 Update

Lisocabtagene maraleucel was approved for the treatment of adult patients with R/R large B cell lymphomas, including DLBCL not otherwise specified, DLBCL arising from indolent lymphoma, high-grade B cell lymphoma, primary mediastinal large B cell lymphoma, and FL grade 3B, who have refractory disease to first-line chemoimmunotherapy, or relapse within 12 months of first-line chemoimmunotherapy as well as later relapse in transplant-ineligible patients in June 2022. Lisocabtagene maraleucel was also approved as third-line or later treatment. [Ref 246]

Axicabtagene ciloleucel was FDA-approved for second-line treatment of large B-cell lymphoma and the treatment of R/R large B cell lymphomas (including DLBCL, PMBCL, HGBCL, and transformed FL) after two or more prior lines of systemic therapy in April 2022. [Ref 111]

Tisagenlecleucel was FDA-approved for the treatment of R/R large B cell lymphomas (including DLBCL not otherwise specified, HGBCL, and DLBCL arising from FL) and FL after two or more prior lines of systemic therapy in May 2022. [Ref 113]

Axicabtagene ciloleucel was FDA-approved for the treatment of R/R FL after two or more lines of systemic therapy in March 2021. [Ref 111]

v1.2 Update

Loncastuximab tesirine received an accelerated approval for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including DLCBCL not otherwise specified, DLBCL arising from low-grade lymphoma, and HGBCL in April 2021. [Ref 260]

v1.3 Update

Revised Recommendation:

• For second-line therapy of DLBCL in patients who are transplant-ineligible, options include lisocabtagene maraleucel, lenalidomide, lenalidomide+tafasitamab-cxix, polatuzumab vedotin-piiq+BR or an appropriate salvage chemoimmunotherapy regimen (including R-GemOx or R-GDP).

v1.4 Update

New Recommendation:

• Lisocabtagene maraleucel is recommended for adult patients with relapsed or refractory CLL or SLL who have received at least 2 prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.

Update v1.4

Table 4 - Food and Drug Administration black box warnings for lymphoma immunotherapies has been updated to include the black box warnings of agents approved since publication of the guideline. See here for revised Table 4.

Update v1.4

Change to 'Since guideline publication, additional types of immunotherapies, such as bispecific antibodies and fusion proteins, have been approved which also carry the risk for CRS, neurotoxicities, and CLS. [244, 249, 252]

v1.4 Update

Lisocabtagene maraleucel received an accelerated approval for adult patients with relapsed or refractory CLL or SLL who have received at least 2 prior lines of therapy, including a BTKi and a B-cell lymphoma 2 BCL-2 inhibitor in March 2024. Approval was based on the primary endpoint ORR data from TRANSCEND-CLL (NCT03331198), a single-arm phase 1/II trial. The ORR for lisocabtagene maraleucel (n=65) was 45% (95% CI 32.3 to 57.5), with a median DOR of 35.3 months (95% CI 12.4 months to NR). Serious AEs occurred in 60% of patients, with CRS occurring at a rate of >20%. [Ref 246, 261].

Update v1.4

Revised Recommendation:

• Denileukin diftitox-cxdl is approved for the treatment of adult patients with R/R stage I-III CTCL after at least one prior systemic therapy. Additional treatment options include HDAC inhibitors, an appropriate chemotherapy regimen (such as pralatrexate), and BV.

v1.4 Update

New Recommendation:

• Mogamulizumab is recommended for the treatment of R/R MF or SS after at least one prior systemic therapy. Additional off-label immunotherapy options include IFN-gamma, pembrolizumab, and alemtuzumab. Non-immunotherapy options include HDAC inhibitors, retinoids, topical therapies, and extracorporeal photopheresis.

v1.4 Update

Revised Recommendation:

• The panel did not reach consensus on a specific treatment regimen for the third-line treatment of PMBCL. Treatment options include axicabtagene ciloleucel, lisocabtagene maraleucel, BV+pembrolizumab, BV + nivolumab, pembrolizumab monotherapy, or appropriate salvage chemotherapy regimens.

v1.4 Update

Revised Recommendation:

• There was consensus that second-line (or later) treatment regimens for patients with MZL will vary, and should be decided on a case-by-case basis using factors that include prior therapies, time of relapse, tumor bulk, age, and comorbidity status, and may consist of lenalidomide with obinutuzumab, zanubrutinib or ibrutinib.

v1.4 Update

Revised Recommendation:

• There was consensus that second-line (or later) treatment regimens for patients with FL will vary, and should be decided on a case-by-case basis using factors that include prior therapies, time of relapse, tumor bulk, age, and comorbidity status. Lenalidomide with obinutuzumab may be used in this context, if deemed appropriate. Lisocabtagene maraleucel is approved for FL grade 3B after two or more lines of systemic therapy. Axicabtagene ciloleucel, tisagenlecleucel, lisocabtagene maraleucel, epcoritamab, mosunetuzumab, and zanubrutinib with obinutuzumab, ibritumomab tiuxetan, and tazemetostat are approved for adult patients with FL after two or more lines of therapy.

v1.4 Update

Revised Recommendation:

• The panel did not reach consensus on second-line or later lines of treatment for patients with MCL. Treatment options include brexucabtagene autoleucel, proteasome inhibitors, BTK inhibitors, BTK inhibitors+rituximab, or lenalidomide+rituximab. Lisocabtagene maraleucel is approved for patients with MCL who have received at least two prior lines of systemic therapy including a BTK inhibitor.

v1.4 Update

Revised Recommendation:

• There was consensus that patients who are ineligible for third-line anti-CD19 CAR T cell therapy should instead receive polatuzumab vedotin-piiq+BR, loncastuximab tesirine, epcoritamab, or glofitamab.

v1.4 Update

Revised recommendation:

• There was consensus that the third-line treatment for DLBCL in fit patients who have not previously received CAR T cell therapy should be anti-CD19 CAR T cell therapy (axicabtagene ciloleucel, lisocabtagene maraleucel, or tisagenlecleucel).

v1.3 Update

Revised Recommendation:

• For the second-line therapy of DLBCL that has relapsed > 12 months after receiving first-line chemoimmunotherapy, transplant-eligible patients should receive a chemoimmunotherapy regimen that includes rituximab (such as rituximab+ICE (R-ICE) or rituximab+dexamethsone+cytarabine+cisplatin (R-DHAP)), followed by autoSCT consolidation if CR is achieved.

v1.4 Update

Revised Recommendation:

• There was consensus that the first-line regimen for newly diagnosed DLBCL in adult patients should be R-CHOP or pola-R-CHP (IPI ≥ 2). Pola-R-CHP showed improved outcomes for patients with ABC subtype.

v1.3 Update

New Recommendation:

• For the second-line therapy of DLBCL that is refractory to first-line chemoimmunotherapy or relapses within 12 months of chemoimmunotherapy, patients should receive axicabtagene ciloleucel or lisocabtagene maraleucel.

v1.4 Update

Revised Recommendation: * For the first-line therapy of stage III–IV cHL, nivolumab-AVD is recommended. If not a candidate for checkpoint inhibitor therapy, A-AVD is the preferred option. If not a candidate for both checkpoint inhibitor therapy and brentuximab vedotin, ABVD is the preferred option.

v1.4 Update

Although not FDA-approved, data for nivolumab + AVD versus BV-AVD for patients with Hodgkin lymphoma have been reported in the phase III SWOG 1826 trial (NCT03907488). For patients treated with nivolumab-AVD (n=487), the median PFS (primary endpoint) was significantly improved in the nivolumab-AVD group (HR for disease progression or death 0.48; 99% CI 0.27 to 0.87; two-sided p=0.001). High-grade AEs were more frequent with BV+AVD, except neutropenia. Hypothyroidism and hyperthyroidism occurred at a rate of 7% and 3%, respectively, in the N+AVD group, compared to <1% and 0%, respectively, in the BV+AVD group. [Ref 255].

Although not FDA-approved, data for nivolumab + chemotherapy and pembrolizumab + chemotherapy for patients with relapsed or refractory Hodgkin lymphoma have been reported in the single-arm phase II trials NCT03016871, NCT03618550, and NCT03077828. In NCT03016871, patients treated with nivolumab (n=34) experienced a CR rate of 71%, while patients treated with nivolumab plus chemotherapy (n=9) experienced a CR rate of 89%. There were no unexpected toxicities observed following nivolumab or nivolumab plus chemotherapy. In NCT03618550, following treatment with pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin (n=38), the CR rate was 95% (95% CI 82% to 99%). Most AEs were grade 1–2 with this treatment. In NCT03077828, following treatment with pembrolizumab in combination with ifosfamide, carboplatin, and etoposide (n=7) the CR rate was 86.5% (95% CI 71.2% to 95.5%). AEs attributed to pembrolizumab treatment occurred in 81% of patients, and grade 3-4 AEs occurred in 52.4% of patients. [Ref 256–258].

v1.4 Update

Since guideline publication, additional immunotherapies have been approved for the treatment of lymphoma, including fusion proteins and bispecific antibodies

This article is part of the special JITC series: Cancer Immunotherapy in Understudied Populations

This article is part of the special JITC series: Computational Immuno-Oncology

Last reviewed 3/19/2024 (v1.1 Update)

SITC continuously evaluates the field for emerging data and new FDA approvals. Updates to the recommendations, tables, treatment algorithms, and/or guideline text in this publication and made with the approval of the SITC NMSC CPG Expert Panel. More information on SITC Guidelines can be found at sitcancer.org/guidelines.

v1.1 Update Summary

• The FDA granted accelerated approval for retifanlimab (anti-PD-1 ICI) for the treatment of adult patients with metastatic or recurrent locally advanced MCC in March 2023. The NMSC CPG was updated in the following locations: Introduction, Merkel Cell Carcinoma, Recommended Immunotherapies for MCC, Figure 1 – FDA-Approved ICI agents for NMSC, Table 2 – NMSC Landmark Clinical Trial Data Leading to FDA Approvals for ICIs for MCC and Novel Strategies and Promising Future Directions. [Ref 177, 178]

• Data have been reported demonstrating efficacy with neoadjuvant anti-PD-1 ICI therapy prior to curative-intent surgery in patients with CSCC. Based on these practice-changing data, the NMSC CPG was updated in the following locations: Based on these practice-changing data, the NMSC CPG was updated in the following locations: Recommended Immunotherapies for CSCC, and Novel Strategies and Promising Future Directions for CSCC. [Ref 179]

• Data have been reported demonstrating efficacy combining an anti-PD-(L)1 ICI with an anti-CTLA-4 ICI for patients with advanced MCC. Based on these practice-changing data, the NMSC CPG was updated in the following locations: Merkel Cell Carcinoma, Recommended Immunotherapies for MCC, and Novel Strategies and Future Directions for CSCC. [Ref 180, 181]

See highlighted text for updated content and more detailed information.

v2.3 Update

Revised recommendation:

• PD-L1 expression by IHC should not be used to guide first-line therapy in patients with mUC.

This article is part of the special JITC series: Cancer Immunotherapy in Understudied Populations

Update v1.1

Based on the FDA approvals for pembrolizumab for patients with recurrent or metastatic cutaneous squamous cell carcinoma [Ref 108, 169] and toripalimab in combination with cisplatin and gemcitabine for first-line treatment of patients with metastatic or recurrent locally advanced nasopharyngeal carcinoma, or as a monotherapy for treatment of adult patients with recurrent, unresectable, or metastatic nasopharyngeal carcinoma with disease progression on or after platinum-containing chemotherapy [Ref 170, 171], the guideline has been updated.

The following recommendations were added or amended:

• Cemiplimab or pembrolizumab, if not contraindicated (eg, organ transplant recipients), should be prescribed for patients with metastatic or locally-advanced cSCC in the head and neck region who are not candidates for curative surgery or radiation, or for whom neoadjuvant response reduces the morbidity of definitive therapy.

• For patients with metastatic or recurrent locally advanced nasopharyngeal carcinoma, first-line treatment with toripalimab in combination with cisplatin and gemcitabine is recommended.

  • There is clinical evidence for other PD-1 inhibitors as well, and these may be substituted if toripalimab is unavailable.

• For patients with recurrent unresectable or metastatic nasopharyngeal carcinoma who have disease progression on or after platinum-containing chemotherapy, toripalimab monotherapy is recommended.

  • There is clinical evidence for other PD-1 inhibitors as well, and these may be substituted if toripalimab is unavailable.

Update v1.1

Based on the practice changing data reported in CheckMate 141 regarding nivolumab as a first-line treatment in R/M HNSCC after progressing on platinum therapy for locally advanced disease in the adjuvant or primary (ie, with radiation) setting [Ref 172], and the practice-changing data reported from the KEYNOTE-B10 and FRAIL-IMMUNE/GORTEC 2018-03 trials regarding anti-PD-1 ICIs in combination with carboplatin + paclitaxel for patients with treatment-naïve R/M HNSCC who are frail and/or not eligible for cisplatin-based therapies [Refs 173, 174], the guideline has been updated.

The following recommendations have been added or revised for 'First-line treatment with PD-1 inhibitors'

Pembrolizumab is indicated for treatment-naïve R/M HNSCC. * Pembrolizumab monotherapy may be used to treat patients with treatment-naïve R/M HNSCC and PD-L1 CPS ≥1. * Pembrolizumab + chemotherapy may be used to treat all patients with treatment-naïve R/M HNSCC. Use of chemotherapy is particularly considered in patients who are symptomatic given the higher ORR for combination pembrolizumab plus chemotherapy. Treatment options include: - Pembrolizumab + chemotherapy (platinum and 5-FU). - If preferred, pembrolizumab plus carboplatin plus paclitaxel may be used as first-line treatment in patients with R/M HNSCC based on the initial results of the phase IV, single-arm, open-label KEYNOTE-B10 study. The GORTEC 2018-03 study supports the combination of weekly carboplatin and paclitaxel with immunotherapy for older patients and those with co-morbidity.

For biomarker-unspecified patients with R/M HNSCC whose disease has progressed within 6 months of platinum-based chemoradiotherapy, pembrolizumab or nivolumab monotherapy may be used.

The following recommendations have been added or revised for 'Second-line treatment with PD-1 inhibitors'

For patients with R/M HNSCC who are platinum-refractory and immunotherapy-naive:

• Pembrolizumab or nivolumab monotherapy should be used.
• If a clinical trial is available, this is the preferred option.

For R/M HNSCC patients with disease progression following ICI monotherapy, clinical trial enrollment or guideline-based standard of care is recommended.

For R/M HNSCC patients with disease progression on or after systemic platinum-based chemotherapy in combination with ICI therapy, clinical trial enrollment or guideline-based standard of care is recommended.

Last Reviewed 11/15/2024 (v1.1 Update)

SITC continuously evaluates the field for practice-changing data and new FDA approvals. The information on this page provides a detailed overview of updates to the guideline content based on changes in the field. Updates to the guideline outlined below were made with the approval of SITC's Head and Neck Squamous Cell Carcinoma (HNSCC) Guideline Expert Panel. More information on SITC Guidelines can be found at sitcancer.org/guidelines.

Update v1.1 Summary * The FDA approved pembrolizumab for patients with recurrent or metastatic cutaneous squamous cell carcinoma in June 2020 [Ref 108, 169].

• The FDA approved toripalimab in combination with cisplatin and gemcitabine for first-line treatment of patients with metastatic or recurrent locally advanced nasopharyngeal carcinoma, or as a monotherapy for treatment of adult patients with recurrent, unresectable, or metastatic nasopharyngeal carcinoma with disease progression on or after platinum-containing chemotherapy in October 2023 [Ref 170, 171].

• Practice-changing data have been reported from CheckMate 141 regarding nivolumab as a first-line treatment in recurrent or metastatic HNSCC after progressing on platinum therapy for locally advanced disease in the adjuvant or primary (ie, with radiation) setting [Ref 172].

• Practice-changing data have been reported from KEYNOTE B10 and the FRAIL-IMMUNE/GORTEC 2018-03 trials, demonstrating efficacy of combining an anti-PD-(L)1 immune checkpoint inhibitor (ICI) with carboplatin + paclitaxel in frail patients with R/M HNSCC [Ref 173, 174].

Update v1.1

The following references have been added:

1. FDA approves pembrolizumab for cutaneous squamous cell carcinoma. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-cutaneous-squamous-cell-carcinoma

2. FDA approves toripalimab-tpzi for nasopharyngeal carcinoma. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-toripalimab-tpzi-nasopharyngeal-carcinoma

3. Food and Drug Administration, Coherus BioSciences. LOQTORZ (toripalimab-tpzi) prescribing information. Available: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=761240 Accessed 6/27/24.

4. Gillison ML, Blumenschein Jr G, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington KJ, Kasper S, Vokes EE, Even C, Worden F, Saba NF, Iglesias Docampo LC, Haddad R, Rordorf T, Kiyota N, Tahara M, Monga M, Lynch M, Li L, Ferris RL. CheckMate 141: 1‐Year Update and Subgroup Analysis of Nivolumab as First‐Line Therapy in Patients with Recurrent/Metastatic Head and Neck Cancer. The Oncologist, 2018 Sept. https://doi.org/10.1634%2Ftheoncologist.2017-0674"10.1634/theoncologist.2017-0674

5. Dzienis MR, Cundom JE, Fuentes CS, Hansen AR, Nordlinger MJ, Pastor AV, Oppelt P, Neki A, Gregg RW, Lima IPF, Franke FA, daCunha Junior GF, Tsent JE, Loree T, Joshi AJ, Mccarthy JS, Naicker N, Sidi Y, Gumuscu B, De Castro Jr G. 651O Pembrolizumab (pembro) + carboplatin (carbo) + paclitaxel (pacli) as first-line (1L) therapy in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): Phase VI KEYNOTE-B10 study. Annals of Oncology, 2022 Sept. https://doi.org/10.1016/j.annonc.2022.07.775

6. Fayette J, Cropet C, Gautier J, Toullec C , Burgy M, Bruyas A, Sire C, Lagrange A, Clatot F, Calderon B, Vinches M, Iacob M, Martin L, Neidhardt Berard EM, Kaminsky MC, Vansteene D, Salas S, Champagnac A, Pérol D, Bourhis J. Results of the multicenter phase II FRAIL-IMMUNE trial evaluating the efficacy and safety of durvalumab combined with weekly paclitaxel carboplatin in first-line in patients (pts) with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) not eligible for cisplatin-based therapies. J Clin Oncol 41, 2023 (suppl 16; abstr 6003).

Figure 2 has been updated. See updated Figure 2.

Update v1.1

Figure 1 has been updated to incorporate FDA-approvals and practice-changing data. See updated Figure 1. [Ref 108, 169, 171-174]

Update v1.1

Some recommendations in Table 1 have been updated to include FDA approvals and practice-changing data that have been reported since publication of this guideline. The updated recommendations can be found in the text overlays and in the updated Table 1 [Ref 108, 169-174].

This supplement is part 2 of 2 supplements published in conjunction with the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting. For access to the other supplement, see below.

SITC 39th Annual Meeting (SITC 2024) Abstracts https://jitc.bmj.com/content/12/Suppl_2

This supplement is part 1 of 2 supplements published in conjunction with the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting. For access to the second supplement, see below.

SITC 39th Annual Meeting (SITC 2024) Late Breaking Abstracts https://jitc.bmj.com/content/12/Suppl_3

v2.4 Update

Table 5 - mUC treatment algorithm has been updated based on the FDA approvals for enfortumumab vedotin + pembrolizumab and for nivolumab in combination with gemcitabine and cisplatin for patients with advanced mUC. See here for revised Table 5 - mUC treatment algorithm [Ref 3, 6, 158].

v2.3 Update

Table 5 - mUC treatment algorithm has been updated based on the label change for pembrolizumab, the voluntary withdrawal of the atezolizumab indication, and the approval of pembrolizumab plus enfortumab vedotin for the treatment of patients with advanced mUC [Ref 3, 158, 161].

v2.4 Update

New Panel recommendation:

• Based on the data demonstrating that FGFR3 mutations are not associated with resistance to PD-(L)1 blockade, patients with metastatic FGFR3-mutant urothelial cancer should not be precluded from receiving anti-PD-(L)1 therapy prior to erdafitinib (LE:2).

v2.3 Update

In August 2021, the indication for pembrolizumab for the treatment of patients with metastatic or locally advanced mUC ineligible for platinum-containing chemotherapy or with disease progression on or after platinum-containing chemotherapy was converted to full approval and revised to no longer specify PD-L1 expression status for eligibility [Ref 3].

In November 2022, the confirmatory trial for the atezolizumab accelerated approval, IMvigor130, did not meet the co-primary endpoint of OS for atezolizumab plus chemotherapy versus chemotherapy alone, and the indication for atezolizumab for the treatment of patients with locally advanced or mUC who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (PD-L1–stained tumor-infiltrating immune cells covering ≥5% of the tumor area) or are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status was voluntarily withdrawn by the manufacturer [Ref 161].

The FDA granted an accelerated approval for pembrolizumab plus enfortumab vedotin for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy in April 2023. Approval was based on ORR and DOR data from the phase II, multi-cohort EV-103/KEYNOTE-869 (NCT03288545) trial, which enrolled patients that had not received prior systemic therapy for locally advanced or metastatic disease and were ineligible for cisplatin-containing chemotherapy. ORR (n = 121) was 68% (95% CI 59% to 76%), DOR for Cohort K (patients randomized to receive either the combination or enfortumab vedotin alone) was NR (range 1 to 24+ months), and DOR for the dose escalation Cohort plus Cohort A (all patients received enfortumab vedotin plus pembrolizumab) was 22 months (range 1+ to 46+). Enfortumab vedotin is also approved as a single agent for patients with locally advanced or metastatic mUC who have previously received an anti-PD-(L)1 ICI and platinum-contain chemotherapy, or who are cisplatin-ineligible and have received one or more prior lines of therapy [Ref 3, 158].

v2.4 Update

Table 2 - NMIBC Immunotherapy treatment algorithm has been updated based on the approval of nogapendekin alfa inbakicept in combination with BCG for the treatment of BCG-unresponsive NMIBC with CIS with or without papillary tumors. See here for revised Table 2 - NMIBC immunotherapy treatment algorithm [Ref 160].

v2.3 Update

Table 2 - NMIBC Immunotherapy treatment algorithm has been updated to include nadofaragene firadenovec as a treatment option for patients with high-risk BCG-unresponsive NMIBC with CIS with or without papillary tumors [Ref 162].

v2.4 Update

In cohort 2 of the randomized phase 2 THOR study (NCT03390504), erdafitinib versus pembrolizumab had similar median overall survival in an anti–PD-(L)1-naive, FGFR-altered population of patients with metastatic urothelial cancer who had progressed despite prior platinum-based chemotherapy [Ref 159]. These results reinforce that FGFR3 mutations are not associated with resistance to PD-(L)1 blockade and that patients with metastatic FGFR3 mutant urothelial cancer should generally receive anti-PD-(L)1 therapy prior to erdafitinib.

v2.3 Update

In August 2021, the indication for pembrolizumab for the treatment of patients with metastatic or locally advanced mUC ineligible for platinum-containing chemotherapy or with disease progression on or after platinum-containing chemotherapy was converted to full approval and revised to no longer specify PD-L1 expression status for eligibility [Ref 3].

In November 2022, the indication for atezolizumab for the treatment of patients with locally advanced or mUC who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (PD-L1–stained tumor-infiltrating immune cells covering ≥5% of the tumor area) or are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status was voluntarily withdrawn by the manufacturer [Ref 161].

v2.4 Update

The following references have been added:

1. Food and Drug Administration (FDA) AP. Enfortumab vedotin (PADVEC) prescribing information. n.d. Available: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=761137

2. Siefker-Radtke A, Matsubara N, Park S, Huddart R, Burgess E, Özgüroğlu M, et al. Erdafitinib versus pembrolizumab in pretreated patients with advanced or metastatic urothelial cancer with select FGFR alterations: cohort 2 of the randomized phase III THOR trial. Annals of Oncology. 2024;35(1):107-17. https://doi.org/10.1016/j.annonc.2023.10.003

3. Food and Drug Administration (FDA) AB. Nogapendekin alfa-inbakicept (ANKTIVA) prescribing information. n.d. Available: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=761336

4. Genentech Provides Update on Tecentriq U.S. Indication for Previously Untreated Metastatic Bladder Cancer. Available: https://www.gene.com/media/statements/ps_112822 Accessed: 9/18/24

5. Food and Drug Administration (FDA) FP. Nadofaragene firadenovec (ADSTILADRIN) prescribing information. n.d. Available: https://www.fda.gov/media/164029/download

6. Chamie K, Chang SS, Kramolowsky E, Gonzalgo ML, Agarwal PK, Bassett JC, et al. IL-15 superagonist NAI in BCG-unresponsive non–muscle-invasive bladder cancer. NEJM evidence. 2022;2(1):EVIDoa2200167. https://doi.org/10.1056/evidoa2200167

7. Powles T, Valderrama BP, Gupta S, Bedke J, Kikuchi E, Hoffman-Censits J, et al. Enfortumab vedotin and pembrolizumab in untreated advanced urothelial cancer. New England Journal of Medicine. 2024;390(10):875-88. https://doi.org/10.1056/nejmoa2312117

8. Van Der Heijden MS, Sonpavde G, Powles T, Necchi A, Burotto M, Schenker M, et al. Nivolumab plus gemcitabine–cisplatin in advanced urothelial carcinoma. New England Journal of Medicine. 2023;389(19):1778-89. https://doi.org/10.1056/nejmoa2309863

Data in this table are as of the time of guideline publication.

v2.4 Update

EV302 (NCT04223856) met its primary end-points, and in December 2023, the FDA approved EV in combination with pembrolizumab for first-line treatment of advanced or mUC [Ref 164].

v2.4 Update

Revised Panel recommendation:

• Pembrolizumab is recommended for the treatment of patients with platinum-refractory mUC who have not received prior ICI treatment based on a significant OS benefit in a randomized phase III trial (LE: 2). Avelumab and nivolumab also have approvals in this setting (LE:3).

v2.4 Update

Revised Panel recommendation:

• For patients with mUC, first-line treatment options include enfortumab vedotin plus pembrolizumab (preferred) regardless of whether patients are cisplatin-eligible or cisplatin-ineligible (LE:2), or gemcitabine, cisplatin, plus nivolumab in patients who are cisplatin-eligible (LE:2). Both of these regimens have been shown to improve OS compared with platinum-based chemotherapy alone.

v2.1 Update

Full approval of nivolumab in this setting was granted in August, 2021 [Ref 6].

v2.3 Update

In November 2022, the confirmatory trial for the atezolizumab accelerated approval, IMvigor130, did not meet the co-primary endpoint of OS and the indication for atezolizumab for first-line treatment of PD-L1-positive mUC in patients who are ineligible for cisplatin-containing chemotherapy or those who are not eligible for any platinum-based chemotherapy, regardless of PD-L1 status, was voluntarily withdrawn by the manufacturer [Ref 161].

Data in this table are as of the time of guideline publication.

v2.2 Update

In August 2021, the indication for pembrolizumab for the treatment of patients with metastatic or locally advanced mUC ineligible for platinum-containing chemotherapy or with disease progression on or after platinum-containing chemotherapy was converted to full approval and revised to no longer specify PD-L1 expression status for eligibility [Ref 3].

v2.3 Update

In November 2022, the confirmatory trial for the atezolizumab accelerated approval, IMvigor130, did not meet the co-primary endpoint of OS and the indication for atezolizumab for first-line treatment of PD-L1-positive mUC in patients who are ineligible for cisplatin-containing chemotherapy or those who are not eligible for any platinum-based chemotherapy, regardless of PD-L1 status, was voluntarily withdrawn by the manufacturer [Ref 161].

v2.4 Update

In addition to the FDA approved first-line treatment regimens mentioned in this section, enfortumab vedotin plus pembrolizumab received accelerated FDA approval in December, 2023 for the treatment of advanced or mUC based on the efficacy data from the phase III EV302 trial (NCT04223856). The median PFS was 12.5 months (95% CI 10.4 to 16.6) for the EV plus pembrolizumab arm (n=442) and 6.3 months (95% CI 6.2 to 6.5) for the chemotherapy group (n=444) (HR = 0.45; p < 0.001). The median OS was also improved in the EV plus pembrolizumab treatment relative to the chemotherapy arm at 31.5 months (95% CI 25.4 to NE) and 16.1 months (95% CI 13.9 to 18.3) respectively (HR = 0.47; p < 0.001). Grade ≥3 treatment related adverse events occurred in 55.9% of patients in the EV plus pembrolizumab group and in 69.5% of patients receiving chemotherapy. [Ref 3, 158, 164].

The FDA also approved nivolumab in combination with gemcitabine and cisplatin for the first-line treatment of patients with unresectable or metastatic UC in March, 2024. This approval was based on efficacy data evaluated in the CheckMate-901 trial. The median OS was longer in patients receiving nivolumab in combination with cisplatin and gemcitabine followed by nivolumab alone (n=304) relative to patients receiving gemcitabine-cisplatin alone (n=304), at 21.7 months (95% CI 18.6 to 26.4) and 18.9 months (95% CI 14.7 to 22.4) respectively (HR = 0.78; p = 0.02). The median PFS was also improved in the patients receiving the nivolumab combination therapy in comparison to gemcitabine-cisplatin treatment, at 7.9 months (95% CI 7.6 to 9.5) and 7.6 months (95% CI 6.1 to 7.8) respectively (HR = 0.72; p = 0.001). Grade ≥3 treatment related adverse events occurred in 61.8% of patients receiving the nivolumab combination treatment and in 51.7% of patients in the gemcitabine-cisplatin group [Ref 6, 165].

v2.4 Update

Since the approvals of enfortumab vedotin + pembrolizumab and nivolumab + cisplatin + gemcitabine for the treatment of advanced mUC, these treatment combinations have become first-line SOC.

v2.1 Update

Recommendation modified to include information on the approval of nivolumab as adjuvant treatment for patients with surgically resected, high-risk MIBC, as noted below:

• For patients with MIBC at high risk for recurrence after radical resection (ypT2-ypT4a or ypN+ for patients who received neoadjuvant cisplatin-based chemotherapy or pT3-pT4a or pN+ for patients who did not receive neoadjuvant cisplatin-based chemotherapy and who also either were ineligible for or refused adjuvant cisplatin-based chemotherapy) adjuvant nivolumab extends DFS as demonstrated in CheckMate 274 (LE: 2). Neoadjuvant therapy with cisplatin-based combination chemotherapy remains the treatment paradigm for curative intent therapy when surgery is considered; the data of CheckMate 274 are insufficient to conclude that adjuvant immunotherapy alone can replace the current practice which is known to maximize survival. Active investigation is ongoing into various additional neoadjuvant and/or adjuvant strategies (and bladder preservation), either as single agents, or in combination with chemotherapy, radiotherapy, or novel agents.

v2.1 Update

Since guideline publication, the FDA approved nivolumab for the adjuvant treatment of patients with urothelial cancer (UC) who are at high risk of recurrence after undergoing radical resection in August 2021 [Ref 6].

v2.3 Update

In December 2022, the FDA approved nadofaragene firadenovec, a non-replicating (cannot multiply in human cells) adenoviral vector based gene therapy indicated for the treatment of adult patients with high-risk BCG-unresponsive NMIBC with CIS with or without papillary tumors [Ref 162].

Approval was based on results from Study CS-003 (NCT02773849), a single-arm study that enrolled 157 patients who had high-risk NMIBC, 98 of whom had BCG-unresponsive disease. The registrational data leading to approval reported a CR rate of 51% (95% CI 41% to 61%) in patients that recieved nadofaragene firadenovec (CR defined as the disappearance of all signs of cancer as seen on cystoscopy, biopsied tissue, and urine). The median DOR was 9.7 months (range 3 to 52+), and 46% remained in CR for at least 1 year [Ref 162].

v2.4 Update

Revised recommendation: * The following treatments are approved for adult patients with Bacillus Calmette Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors: pembrolizumab monotherapy (LE:2), nadofaragene firadenovec-vcng monotherapy (LE:2), or nogapendekin alfa inbakicept-pmln in combination with BCG. The decision as to which of these agents should be used should be based on shared decision making, taking into account factors such as efficacy, adverse events and also patient preferences regarding scheduling and administration routes.

v2.4 Update

Nogapendekin alfa-inbakicept (NAI), an interleukin 15 (IL-15) superagonist, gained FDA approval in April, 2024 as a combination treatment with BCG for the treatment of adult patients with BCG-unresponsive NMIBC with CIS with or without papillary tumors. Approval was based on complete response data from QUILT-3.032 (NCT0302285), a single-arm, multicenter trial that enrolled 77 patients (cohort A) with BCG-unresponsive, high-risk NMIBC with CIS with or without papillary tumors to receive NAI in combination with BCG. Complete response at any time (assessed every 3 months for up to 2 years) was reported in 62% (95% CI 51% to 73%) of patients, with 58% of complete responders having a DOR ≥ 12 months and 40% of complete responders having a DOR ≥ 24 months. Serious adverse reactions occurred in 16% of patients, with the most common adverse reaction being hematuria (3.4%) [Ref 160, 163].

v2.3 Update

In December 2022, the FDA approved nadofaragene firadenovec, a non-replicating (cannot multiply in human cells) adenoviral vector based gene therapy indicated for the treatment of adult patients with high-risk BCG-unresponsive NMIBC with CIS with or without papillary tumors. [Ref 162].

Last Reviewed 10/19/2024 (v2.4 Update)

SITC continuously evaluates the field for emerging data and new FDA approvals. Updates to the recommendations, tables, treatment algorithms, and/or guideline text in this publication are made with the approval of the SITC Urothelial Cancer Immunotherapy Guideline Expert Panel. More information on the SITC Guidelines can be found at sitcancer.org/guidelines.

v2.4 Update Summary

• The FDA granted accelerated approval of enfortumab vedotin in combination with pembrolizumab for the treatment of adult patients with locally advanced or metastatic urothelial cancer in December 2023 [Ref 3, 158].

• The FDA granted approval of nivolumab in combination with cisplatin and gemcitabine as first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma in March 2024 [Ref 6].

• Data have been reported indicating similar responses to ICI therapy regardless of FGFR3 mutation status for patients with metastatic urothelial cancer [Ref 159].

• The FDA granted approval of nogapendekin alfa inbakicept with BCG for adult patients with BCG-unreseponsive NMIBC with carcinoma in situ with or without papillary tumors in April 2024 [Ref 160].

v2.3 Update Summary

• Atezoluzimab for the treatment of cisplatin- and platinum-ineligible patients with mUC was voluntary withdrawn by the manufacturer in November, 2022 [Ref 161].

• The FDA granted approval of nadofaragene firadenovec for the treatment of BCG-unresponsive NMIBC with CIS with or without papillary tumors in December 2022 [Ref 162].

• The FDA granted accelerated approval of enfortumab vedotin with pembrolizumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy in April 2023 [Ref 3, 158].

v2.2 Update Summary * The indication of pembrolizumab for the treatment of patients with mUC ineligible for platinum-containing chemotherapy or with disease progression on or after platinum-containing chemotherapy was revised in August 2021 to no longer specify PD-L1 status for eligibility [Ref 3].

v2.1 Update Summary * The FDA granted approval of nivolumab for the treatment of patients with urothelial cancer who are at high risk of recurrence after undergoing radical resection in August 2021 [Ref 6].

See the highlighted text for updated content and more detailed information.

This article is part of the special JITC series: The Next Wave of Immuno-oncology: A Roadmap from the Society for Immunotherapy of Cancer (SITC)

This article is part of the special JITC series: SITC 40th Anniversary: I-O Progress and Potential

This article is part of the special JITC series: Computational Immuno-Oncology

This article is part of the special JITC series: Cancer Immunotherapy in Understudied Populations

This article is part of the special JITC series: Cancer Immunotherapy in Understudied Populations

This article is part of the special JITC series: Cancer Immunotherapy in Understudied Populations

As supplementary material to Addendum 1 (update v1.1(A)), SITC has created a treatment algorithm for HCC.

Last reviewed 6/16/23 (v1.1(A) update supplement)

SITC continuously evaluates the field for emerging data and new FDA approvals. Updates to the recommendations, tables, treatment algorithms, and/or guideline text in this publication are made with the approval of the SITC HCC CPG Expert Panel. More information on SITC Guidelines can be found at sitcancer.org/guidelines.

SITC published an addendum to the guideline (Addendum 1, update v1.1(A)) based on the approval of tremelimumab in combination with durvalumab for adult patients with unresectable HCC. A supplementary immunotherapy treatment algorithm for HCC was generated based on the Expert Panel recommendations. It can be found on the SITC website here.

View the supplement to this addendum "HCC Immunotherapy Treatment Algorithm" on the SITC website.

Last reviewed 6/16/23 (v1.1(A) update supplement)

SITC continuously evaluates the field for emerging data and new FDA approvals. Updates to the recommendations, tables, treatment algorithms, and/or guideline text in this publication are made with the approval of the SITC HCC CPG Expert Panel. More information on SITC Guidelines can be found at sitcancer.org/guidelines.

A supplementary immunotherapy treatment algorithm for HCC was generated based on the Expert Panel recommendations. It can be found on the SITC website here.

Update v1.1

New Recommendation: * For patients with FIGO 2014 stage III-IVA cervical cancer, pembrolizumab plus chemoradiotherapy is recommended.

Update v1.1

Table 2 has been revised to include trial data from KEYNOTE-A18 (NCT04221945) that led to the approval of pembrolizumab plus chemoradiotherapy for patients with FIGO stage III-IVA cervical cancer. Updated Table 2 can be found here.

Update v1.1

In addition to the approved ICI-based regimens described in this section, since guideline publication pembrolizumab with chemoradiotherapy was granted FDA approval for patients with FIGO 2014 stage III-IVA cervical cancer on January 12, 2024. Approval was based on the KEYNOTE-A18 (NCT04221945) trial. The primary outcome measures for approval were PFS and OS. Grade ≥ 3 TRAEs and any-grade irAEs occurred in 67% and 32% of patients in the pembrolizumab group, respectively. More information on the trial details can be found in the updated Table 2. [Ref 13, 299, 300]

Update v1.1

The following references have been added:

1. US Food and Drug Administration. FDA grants approval for pembrolizumab with chemoradiotherapy (CRT) for patients with FIGO 2014 Stage III-IVA cervical cancer on 2024 January 12. Accessed 5/24/24.https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-chemoradiotherapy-figo-2014-stage-iii-iva-cervical-cancer

2. Lorusso D, Xiang Y, Hasagawa K, et al. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial. The Lancet. 2024;403: 1341-1350.

3. US Food and Drug Administration. FDA grants approval for Dostarlimab (Jemperli, GlaxoSmithKline) + chemo for dMMR endometrial cancer. 2023 July 31. Accessed 5/24/24. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-dostarlimab-gxly-chemotherapy-endometrial-cancer

Update v1.1

Revised Recommendation: * For first-line treatment of recurrent or metastatic endometrial cancer, carboplatin plus paclitaxel with or without trastuzumab (if HER2+ serous endometrial cancer) was the standard of care at the time of guideline publication (LE:2). Anti-PD-1 ICIs in combination with carboplatin plus paclitaxel demonstrated statistically significant and clinically meaningful improvements in PFS over chemotherapy alone for the treatment of previously untreated stage III or IV or first recurrent (after prior neoadjuvant or adjuvant chemotherapy) endometrial cancer. The observed benefit was regardless of MMR status (LE:2).

**Update v1.1 **

Table 3 has been revised to include trial data from RUBY (NCT03981796) that led to the approval of dostarlimab plus carboplatin and paclitaxel for patients with dMMR or MSI-H primary advanced or recurrent endometrial cancer. Updated Table 3 can be found here.

Update v1.1

Since guideline publication, dostarlimab with carboplatin and paclitaxel was FDA-approved for treatment of dMMR or MSI-H (as determined by an FDA-approved test) primary advanced or recurrent endometrial cancer on July 31, 2023. Approval was based on the RUBY (NCT03981796) trial, where the primary outcome measure was PFS. Grade ≥3 adverse events and immune-related events (any grade) related to a trial drug or placebo occured in 50.6% and 38.2% of patients in the dostarlimab group, respectively. More information on trial details can be found in Table 3 [Ref 15, 121, 301]

Update v1.1

Since guideline publication, pembrolizumab in combination with chemoradiotherapy was FDA-approved for patients with FIGO 2014 stage III-IVA cervical cancer [Ref 299].

This article is part of the special JITC series: Computational Immuno-Oncology

v1.1 Update

The following references have been added:

1. US Food and Drug Administration. FDA grants accelerated approval to retifanlimab-dlwr for metastatic or recurrent locally advanced Merkel cell carcinoma. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-retifanlimab-dlwr-metastatic-or-recurrent-locally-advanced-merkel

2. Food and Drug Administration, Incyte Corp. ZYNYZ (retifanlimab) prescribing information: Available: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=761334. Accessed 2/28/24.

3. Gross ND, Miller DM, Khushalani NI, Divi V, Ruiz ES, Lipson EJ, Meier F, Su YB, Swiecicki PL, Atlas J, Geiger JL. Neoadjuvant cemiplimab for stage II to IV cutaneous squamous-cell carcinoma. New England Journal of Medicine. 2022 Oct 27;387(17):1557-68. https://www.nejm.org/doi/10.1056/NEJMoa2209813

4. Bhatia S, Topalian SL, Sharfman WH, Meyer T, Lao CD, Fariñas-Madrid L, Devriese LA, Aljumaily R, Ferris RL, Honma Y, Khan TA. Non-comparative, open-label, international, multicenter phase I/II study of nivolumab (NIVO)±ipilimumab (IPI) in patients (pts) with recurrent/metastatic merkel cell carcinoma (MCC)(CheckMate 358). https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.9506

5. Kim S, Wuthrick E, Blakaj D, Eroglu Z, Verschraegen C, Thapa R, Mills M, Dibs K, Liveringhouse C, Russell J, Caudell JJ. Combined nivolumab and ipilimumab with or without stereotactic body radiation therapy for advanced Merkel cell carcinoma: a randomised, open label, phase 2 trial. The Lancet. 2022 Sep 24;400(10357):1008-19. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)01659-2/abstract

v1.1 Update

Revised Panel recommendation:

• For patients with resectable CSCC at high-risk of recurrence, neoadjuvant anti-PD-1 therapy may be considered for carefully selected patients. Enrollment in clinical trials of neoadjuvant or adjuvant therapy should be offered where available.

v1.1 Update

New Panel recommendation: * Neoadjuvant anti-PD-1 therapy prior to curative-intent surgery was associated with a pCR rate of 51% and a major pathologic response rate of 13% in 70 patients with resectable stage II, III, or IV (M0) CSCC in a phase II study (LE:3). Notably, an additional 9 patients were treated but did not undergo surgery. Although not FDA-approved in this setting, neoadjuvant therapy may be considered for carefully selected patients.

v1.1 Update

Additionally, although not FDA-approved, two studies combining an anti-PD-(L)1 ICI with an anti-CTLA-4 ICI have reported efficacy in patients with recurrent/metastatic MCC. See the Recommended Immunotherapies for MCC section for more information. [Ref 180, 181].

v1.1 Update

Since guideline publication, this phase II study assessing neoadjuvant cemiplimab reported a pCR rate of 51% and a major pathologic response rate of 13% in 70 patients with resectable stage II, III, or IV (M0) CSCC. Notably, an additional 9 patients were treated but did not undergo surgery. (This regimen is not currently FDA-approved). [Ref 179]

v1.1 Update

In addition to the FDA-approved ICIs described in this section, since guideline publication, neoadjuvant anti-PD-1 therapy prior to curative-intent surgery demonstrated efficacy in a phase II study. (This regimen is not currently FDA-approved.) [Ref 179]

v1.1 Update

Since guideline publication, dual ICI therapy (anti-PD-1 + anti-CTLA-4 ICIs) has been tested in two studies of patients with recurrent/metastatic MCC. In a randomized phase II study of 50 patients, nivolumab plus ipilimumab demonstrated a 100% ORR in 24 ICI-naïve patients with unresectable, recurrent, or stage IV MCC, and an ORR of 31% in 26 patients with previous anti-PD-(L)1 therapy. In a non-randomized multicenter study of ICI-naïve patients (CheckMate 358), 68 patients received nivolumab (n = 25) or nivolumab plus ipilimumab (n = 43). The ORR was 60.0% (95% CI 38.7% to 78.9%) in the nivolumab arm and 58.1% (95% CI 42.1% to 73.0%) in the nivolumab plus ipilimumab arm. [Ref 180, 181]

v1.1 Update

Retifanlimab (an anti-PD-1 ICI) was also granted an accelerated approval by the FDA in March 2023 for the treatment of adult patients with metastatic or recurrent locally advanced MCC [Ref 177, 178].

v1.1 Update

Retifanlimab (an anti-PD-1 ICI) was also granted an accelerated approval by the FDA in March 2023 for the treatment of adult patients with metastatic or recurrent locally advanced MCC [Ref 177, 178].

v1.1 Update

Revised Panel recommendation: * For patients with MCC who experience disease progression while on anti-PD-(L)1 immunotherapy, therapeutic options are limited and include the addition of an anti-CTLA-4 antibody to anti-PD-(L)1 therapy, clinical trials, or chemotherapy. Switching treatments from one anti-PD-(L)1 antibody to another anti-PD-(L)1 antibody is unlikely to be beneficial.

v1.1 Update

New Panel recommendation: * Dual ICI therapy (anti-PD-1 + anti-CTLA-4 ICIs) has been tested in two studies of patients with recurrent/metastatic MCC. In a randomized phase II study of 50 patients, nivolumab plus ipilimumab demonstrated a 100% ORR in 24 ICI-naïve patients with unresectable, recurrent, or stage IV MCC, and an ORR of 31% in 26 patients with previous anti-PD-(L)1 therapy (LE:3). In a non-randomized multicenter study of ICI-naïve patients (CheckMate 358), 68 patients received nivolumab (n = 25) or nivolumab plus ipilimumab (n = 43). The ORR was 60.0% (95% CI 38.7% to 78.9%) in the nivolumab arm and 58.1% (95% CI 42.1% to 73.0%) in the nivolumab plus ipilimumab arm (LE:3). This combination is not FDA-approved for MCC, but it is reasonable to consider for select patients, especially in the PD-(L)1-refractory setting. Risk for increased toxicity with the addition of an anti-CTLA-4 agent must be carefully weighed against potential benefits in discussing dual ICI therapy with patients.

v1.1 Update

Table 2 has been updated to include the POD1UM-201 trial information and data for retifanlimab approval. See here for revised Table 2. [Ref 177, 178]

v1.1 Update

In addition to the approved ICIs for MCC described in this section, since guideline publication retifanlimab was granted accelerated approval by the FDA in March 2023 for the treatment of metastatic or recurrent locally advanced MCC. Approval was based on the POD1UM-201 trial (NCT03599713). The primary outcome measures for approval were ORR and DOR (Table 2). Safety was assessed in 105 patients with MCC, where retifanlimab was determined to be safe and well-tolerated. Serious AEs occurred in 22% of patients, and the most common serious AEs were fatigue, arrhythmia, and pneumonitis. Permanent discontinuation of therapy due to AEs occurred in 11% of patients. [Ref 177, 178]

Additionally, although not FDA-approved, two studies combining an anti-PD-(L)1 ICI with an anti-CTLA-4 ICI have reported efficacy in patients with recurrent/metastatic MCC. [Ref 180, 181]

v1.1 Update

Figure 1 has been updated to include retifanlimab as an FDA-approved ICI treatment option for patients with MCC. See updated Figure 1. [Ref 177, 178]

v1.1 Update

Retifanlimab (an anti-PD-1 ICI) was also granted an accelerated approval by the FDA in March 2023 for the treatment of adult patients with metastatic or recurrent locally advanced MCC [Ref 177, 178].

v1.1 Update

Retifanlimab (an anti-PD-1 ICI) was also granted an accelerated approval by the FDA in March 2023 for the treatment of adult patients with metastatic or recurrent locally advanced MCC [Ref 177, 178].

Additionally, although not FDA-approved, two studies combining an anti-PD-(L)1 ICI with an anti-CTLA-4 ICI have reported efficacy in patients with recurrent/metastatic MCC [Ref 180, 181].

v1.1 Update

Retifanlimab (an anti-PD-1 ICI) was also granted an accelerated approval by the FDA in March 2023 for the treatment of adult patients with metastatic or recurrent locally advanced MCC [Ref 177, 178].

v1.2 Update The following references have been added:

1. US Food and Drug Administration. FDA grants accelerated approval to dostarlimab-gxly for dMMR advanced solid tumors. US Food and Drug Administration. 2021. Accessed 2/29/24. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-dostarlimab-gxly-dmmr-advanced-solid-tumors

2. US Food and Drug Administration. List of cleared or approved companion diagnostic devices (in vitro and imaging tools). Accessed 2/29/24 https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools

3. US Food and Drug Administration. FDA grants accelerated approval to pembrolizumab for first tissue/site agnostic indication. Accessed 2/29/24: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pembrolizumab-first-tissuesite-agnostic-indication

4. André T, Berton D, Curigliano G, Sabatier R, Tinker AV, Oaknin A, Ellard S, de Braud F, Arkenau HT, Trigo J, Gravina A. Antitumor activity and safety of dostarlimab monotherapy in patients with mismatch repair deficient solid tumors: a nonrandomized controlled trial. JAMA Network Open. 2023 Nov 1;6(11):e2341165-. https://pubmed.ncbi.nlm.nih.gov/37917058/

v1.2 Update

The FoundationOne CDx assay was approved as the companion diagnostic to identify patients with MSI-H solid tumors for pembrolizumab treatment eligibility in February 2022. [Ref 291]

v1.2 Update

Revised Panel recommendation: * Distant metastatic or recurrent tumor biopsy biomarker assessment should be considered at first relapse, including repeat receptor profiles (ER/PR/HER2), PD-L1 status, and NGS. IHC for MMR can also be considered.

v1.2 Update

Assessment of TMB, MMR, and MSI can also be considered in metastatic or recurrent lesions at first relapse to determine eligibility for the tissue-agnostic indications for pembrolizumab and dostarlimab.

v1.2 Update

Pembrolizumb and dostarlimab, were also approved in tissue-agnostic indications for the treatment of recurrent or advanced/metastatic solid tumors that are dMMR and have progressed on or following prior treatment with no satisfactory alternative treatment options in May 2017 and August 2021, respectively. [Ref 290-293]

v1.2 Update

New Panel recommendation: * For patients with recurrent or advanced dMMR breast cancer that has progressed on or following previous treatment, single agent dostarlimab or pembrolizumab may be considered (understanding that there is limited experience with breast cancer at this time).

v1.2 Update

Pembrolizumab and dostarlimab have also received FDA approvals for tissue-agnositc use for deficient mismatch repair (dMMR; as determined by an FDA-approved test) unresectable/metastatic or recurrent or advanced solid tumors, respectively, that have progressed following prior treatment and who have no satisfactory alternative treatment options. [Ref 290-292]

v1.2 Update

Table 2 has been updated to include the GARNET trial data for dostarlimab tissue agnostic approval. Updated table can be found here: [Table 2] (https://higherlogicdownload.s3.amazonaws.com/SITCANCER/2c19e5a6-3adb-4d01-b46c-c01e11745b3a/UploadedImages/CPG/SITC_Breast_CPG_v1_2_-Table_2_for_JITC_overlay__3-19-24.pdf) [Ref 290]

v1.2 Update

In addition to the approved tissue-agnostic ICI indications described in this section, since guideline publication, dostarlimab was also FDA-approved for the treatment of recurrent or advanced dMMR solid tumors that have progressed on prior therapy with no other satisfactory alternative treatment options, regardless of tissue of origin in August 2021. [Ref 290]

v1.2 Update

Dostarlimab was also granted an accelerated approval for the treatment of adult patients with dMMR recurrent or advanced solid tumors that have progressed on or following prior treatment and who have no satisfactory alternative treatment options in August 2021. Approval was based on results of the GARNET trial (NCT02715284) where 209 patients with dMMR recurrent or advanced solid tumors had an ORR of 41.6% (95% CI 34.9 to 48.6) and a median DOR of 34.7 months (range 2.6 to 35.8+). One patient with breast cancer was represented in the population assessed for approval, demonstrating a complete response. [Ref 290] Since approval of dostarlimab, an interim analysis with longer follow-up has been published. [Ref 293]

The FoundationOne CDx assay is the approved companion diagnostic for assessing MSI status for tissue-agnostic eligibility for pembrolizumab. [Ref 291]

The VENTANA MMR RxDx panel is the approved companion diagnostic for assessing MMR status for tissue-agnostic eligibility for both pembrolizumab and dostarlimab. [Ref 291]

This article is part of the special JITC series: Computational Immuno-Oncology

This article is part of the special JITC series: Computational Immuno-Oncology

This article is part of the special JITC series: Computational Immuno-Oncology

Correction underway

The dosage unit g/kg should read mg/kg for infliximab*. This unit was erroneously updated while previously correcting the dosing for IVIG and is now undergoing formal correction.

*Andruska N, Mahapatra L, Hebbard C, et al. Severe pneumonitis refractory to steroids following anti-PD-1 immunotherapy. BMJ Case Rep 2018;366:bcr-2018.doi:10.1136/bcr-2018-225937 pmid:http://www.ncbi.nlm.nih.gov/pubmed/30301729

Correction underway

The dosage unit g/kg should read mg/kg for infliximab*. This unit was erroneously updated while previously correcting the dosing for IVIG and is now undergoing formal correction.

*Andruska N, Mahapatra L, Hebbard C, et al. Severe pneumonitis refractory to steroids following anti-PD-1 immunotherapy. BMJ Case Rep 2018;366:bcr-2018.doi:10.1136/bcr-2018-225937 pmid:http://www.ncbi.nlm.nih.gov/pubmed/30301729

Correction underway

The dosage unit g/kg should read mg/kg for infliximab*. This unit was erroneously updated while previously correcting the dosing for IVIG and is now undergoing formal correction.

*Andruska N, Mahapatra L, Hebbard C, et al. Severe pneumonitis refractory to steroids following anti-PD-1 immunotherapy. BMJ Case Rep 2018;366:bcr-2018.doi:10.1136/bcr-2018-225937 pmid:http://www.ncbi.nlm.nih.gov/pubmed/30301729

This supplement is part 1 of 2 supplements published in conjunction with the Society for Immunotherapy of Cancer (SITC) 38th Annual Meeting. For access to the second supplement, see below.

SITC 38th Annual Meeting (SITC 2023) Abstracts Supplement 2 https://jitc.bmj.com/content/11/Suppl_2

This supplement is part 2 of 2 supplements published in conjunction with the Society for Immunotherapy of Cancer (SITC) 38th Annual Meeting. For access to the first supplement, see below.

SITC 38th Annual Meeting (SITC 2023) Abstracts https://jitc.bmj.com/content/11/Suppl_1

Update 4-7-21

Figure 1 description has been updated, as noted below:

• Prostate carcinoma treatment algorithm: Reading from left to right, patient populations are identified. Options for treatment strategies for specific patient populations are provided in the right-most column in the corresponding row(s). All options provided are of equal preference, and selection of a treatment strategy should take into account patient- and provider-specific considerations as well as the best clinical judgement of the treating physician.

The Prostate Cancer Treatment Algorithm presented in Figure 1 has been updated in multiple areas, as noted below:

Newly Diagnosed -> Metastatic * ADT + Docetaxel * ADT + Enzalutamide * ADT + Abiraterone * ADT + Apalutamide

Recurrent ADT naïve -> Non-metastatic * ADT * Clinical trials

Recurrent ADT naïve -> Metastatic * ADT * ADT + Docetaxel * ADT + Enzalutamide * ADT + Abiraterone

CRPC -> Non-metastatic * ADT + Darolutamide * ADT + Apalutamide * ADT + Enzalutamide

mCRPC* > Minimal/no symptoms * Sipuleucel-T

mCRPC* -> Symptomatic bone-metastases * Radium-23

mCRPC* -> Symptomatic or asymptomatic * Enzalutamide * Abiraterone * Docetaxel * Clinical trial

mCRPC* -> Post-abiraterone or post-enzalutamide * Olaparib(%)

mCRPC* -> Post-docetaxel * Cabazitaxel * Rucaparib(#)

Updated treatment table

Figure 1 footnotes have been updated, as noted below:

• Although not available at the time of publication, for patients with TMB-H or MSI-H/dMMR tumors, pembrolizumab or dostarlimab may be considered, based on FDA-approved indications. (1) Metastasis defined by positive technetium bone scan or CT scan

(*) Treatment with continuous testosterone suppression, and with or without denosumab or zoledronic acid

(#) Patients with deleterious germline or somatic BRCA mutation who have been treated with taxane-based chemotherapy

(%) Patients with deleterious or suspected deleterious germline or somatic homologous recombination repair gene mutation who have progressed after treatment with enzalutamide or abiraterone

This article is part of the special JITC series: Microbial-Based Cancer Immunotherapy

This article is part of the special JITC series: Microbial-Based Cancer Immunotherapy

This article is part of the special JITC series: Microbial-Based Cancer Immunotherapy

This article is part of the special JITC series: Microbial-Based Cancer Immunotherapy

This article is part of the special JITC series: Immune Monitoring Technology Primers

This article is part of the special JITC series: Immune Monitoring Technology Primers

This article is part of the special JITC series: Immune Monitoring Technology Primers

This article is part of the special JITC series: Immune Monitoring Technology Primers

This article is part of the special JITC series: Immune Monitoring Technology Primers

This article is part of the special JITC series: Immune Monitoring Technology Primers

This article is part of the special JITC series: Immune Monitoring Technology Primers

This article is part of the special JITC series: Immune Monitoring Technology Primers

This article is part of the special JITC series: Immune Monitoring Technology Primers

This article is part of the special JITC series: Immune Monitoring Technology Primers

This article is part of the special JITC series: Immune Monitoring Technology Primers

This article is part of the special JITC series: Immune Monitoring Technology Primers

This article is part of the special JITC series: Emerging Immunotherapeutic Agents

This article is part of the special JITC series: Emerging Immunotherapeutic Agents

This article is part of the special JITC series: Emerging Immunotherapeutic Agents

This article is part of the special JITC series: Emerging Immunotherapeutic Agents

This article is part of the special JITC series: Emerging Immunotherapeutic Agents

This article is part of the special JITC series: Emerging Immunotherapeutic Agents

This article is part of the special JITC series: Immune Checkpoints Beyond PD-1

This article is part of the special JITC series: Immune Checkpoints Beyond PD-1

This article is part of the special JITC series: Immune Checkpoints Beyond PD-1

This article is part of the special JITC series: Immune Checkpoints Beyond PD-1

This article is part of the special JITC series: Immune Checkpoints Beyond PD-1

This article is part of the special JITC series: Immune Checkpoints Beyond PD-1

This article is part of the special JITC series: Immune Checkpoints Beyond PD-1

This article is part of the special JITC series: Immune Checkpoints Beyond PD-1

This article is part of the special JITC series: COVID-19 and Cancer Immunotherapy