Available agents and indications
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]