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

An update to the SITC Lymphoma CPG is currently in preparation to address practice-changing data and new FDA approvals of immune checkpoint inhibitors, CAR T cell therapies, antibody-drug conjugates, monoclonal antibodies, bispecific T cell engagers, immunomodulatory agents, and a cytotoxic recombinant protein. These approvals and practice-changing data will affect the recommendations across a variety of disease states within this guideline.

Update 10-22-2022

Based on the approval of axicabtagene ciloleucel for adult patients with large B-cell lymphoma (LBCL) that is refractory to first-line chemoimmunotherapy or relapses within 12 months of first-line chemoimmunotherapy, the Lymphoma CPG has been updated in the following locations: * Available Agents and Indications for NHL * Expert Panel Recommendations for NHL * Expert Panel Recommendations for NHL

Reference: Axicabtagene ciloleucel (YESCARTA) FDA press release

Based on the approval of tisagenlecleucel for the treatment of adult patients with relapsed or refractory follicular lymphoma following 2 or more lines of systemic therapy, the Lymphoma CPG has been updated in the following location: * Available Agents and Indications for NHL

Reference: Tisagenlecleucel (KYMRIAH) FDA press release

Based on the approval of lisocabtagene maraleucel for the treatment of adult patients with large B-cell lymphoma (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, the Lymphoma CPG has been updated in the following location: * Available Agents and Indications for NHL

Reference: Lisocabtagene maraleucel (BREYANZI) FDA press release

Update 6-3-2021

Based on the approval of loncastuximab tesirine-lpyl for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low grade lymphoma, and high-grade B-cell lymphoma, the Lymphoma CPG has been updated in the following location: * Available Agents and Indications for NHL

Reference: Loncastuximab tesirine-lpyl (ZYNLONTA) FDA press release

Update 2-9-2021

The Lymphoma CPG has been updated in the following location: * Immunotherapies in Development for NHL * Expert Panel Recommendations for NHL

Update 2-9-2021

Immunotherapies in Development for NHL table updated to remove lisocabtagene maraleucel from list of agents in development.

The following row describing TRANSCEND-NHL-001 has been removed from the table "Immunotherapies in development for the treatment of non-Hodgkin lymphoma":

• TRANSCEND-NHL-001 (NCT02631044)
• Agents Investigated: Lisocabtagene maraleucel
• Agent Description: CAR T cell
• Primary Outcome for Assessment: Treatment-related AEs, dose-limiting toxicities, ORR

Update 2-9-2021

Recommendation updated to include lisocabtagene maraleucel as a third-line treatment option for PMBCL, as noted below:

• 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, or appropriate salvage chemotherapy regimens.

Update 10-22-2022

Recommendation updated to reflect the approval of lisocabtagene maraleucel and tisagenlecleucel as a third-line treatments for follicular lymphoma, as noted below:

• 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. Ibritumomab tiuxetan 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 and tisagenlecleucel are approved for adult patients with FL after two or more lines of therapy.

Update 2-9-2021

Recommendation updated to include lisocabtagene maraleucel as third-line treatment option for DLBCL, as noted below:

• There was consensus that the third-line treatment for DLBCL in fit patients should be anti-CD19 CAR T cell therapy (axicabtagene ciloleucel, lisocabtagene maraleucel, or tisagenlecleucel).

Update 10-22-2022

Recommendation updated to reflect the approval of lisocabtagene maraleucel as a second-line treatment for transplant-ineligible patients with DLBCL, as noted below:

• 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).

Update 10-22-2022

Recommendation updated to reflect the appropriate setting for non-CAR T cell options as second-line treatments for refractory DLBCL, as noted below:

• 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.

Update 10-22-2022

Recommendation added for second-line use of axicabtagene ciloleucel and lisocabtagene maraleucel, as noted below:

• 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.

Update 10-22-2022

Description of tisagenlecleucel updated to include disease states specified in FDA approval, including the addition of follicular lymphoma, as noted below:

• Tisagenlecleucel is FDA-approved for the treatment of R/R large B cell lymphomas (including DLBCL not otherwise specified, high grade B cell lymphoma, and DLBCL arising from FL) and FL after two or more prior lines of systemic therapy.

Update 10-22-2022

Description of axicabtagene ciloleucel approved indications updated to include second-line treatment of large B-cell lymphoma, as noted below:

• Axicabtagene ciloleucel is FDA-approved for second-line treatment of large B-cell lymphoma and the treatment of R/R large B cell lymphomas (including DLBCL, PMBCL, high-grade B cell lymphoma, and transformed FL) after two or more prior lines of systemic therapy.

Update 10-22-2022

Description of lisocabtagene maraleucel approvals and indications added, as noted below:

• Lisocabtagene maraleucel is approved for the treatment of 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. Lisocabtagene maraleucel is also approved as third-line or later treatment.

Update 6-3-2021

Description of loncastuximab tesirine-lpyl approval and indication added, as noted below:

• On April 23, 2021, the a CD19-directed antibody and alkylating agent conjugate loncastuximab tesirine-lpyl received 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 high-grade B-cell lymphoma.