Session: 623. Mantle Cell, Follicular, Waldenstrom’s, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical trials, Combination therapy, Adult, Lymphomas, Non-Hodgkin lymphoma, Bispecific Antibody Therapy, Clinical Research, B Cell lymphoma, Diseases, Indolent lymphoma, Treatment Considerations, Biological therapies, Lymphoid Malignancies, Study Population, Human
Methods: Adults with 1L CD20+ FL grade 1–3A received subcutaneous epcoritamab + BR for 6 cycles (Cs; 28 d each) followed by epcoritamab monotherapy. Epcoritamab was administered with a 2-step (0.16 mg and 0.8 mg) step-up dosing regimen in C1 followed by 48-mg full doses (QW in C1–3, Q2W in C4–9, and Q4W thereafter for up to 2 y). The primary endpoint was ORR by PET-CT per Lugano criteria.
Results: At data cutoff (May 15, 2024), 25 pts were treated with 48 mg epcoritamab + BR. The median age was 56 y (range, 32–80), median time from initial diagnosis to first dose of epcoritamab was 9 wk (range, 2–359), and median number of Cs of epcoritamab initiated was 20 (range, 3–26). Most pts had grade 2 (52%) or 3A (40%) FL; 48% and 52% had stage III and IV disease, respectively. With a median follow-up of 30.4 mo (range, 11.7–33.9+), 22 pts (88%) completed 6 Cs of epcoritamab + BR, 11 (44%) completed the full 2 y of tx, and 14 (56%) discontinued tx (progressive disease, n=1; AEs, n=9; pt withdrawal, n=3; and other reason, n=1 [investigator decision, long COVID-19]). Median relative dose intensity of BR was 99%.
ORR and CR rate were both 96%. At 30 mo, an estimated 87% of responders/complete responders remained in response/CR, and estimated progression-free survival (PFS) and overall survival (OS) rates were 83% and 96%, respectively.
With the majority of pts being enrolled and treated during the global COVID-19 pandemic, the most common tx-emergent AE (TEAE) was COVID-19 (72%), which led to discontinuation of epcoritamab in 7 pts (COVID-19, n=6; post-acute COVID-19 syndrome, n=1); there was 1 grade 5 COVID-19 TEAE. The next most common TEAEs were CRS (68%), nausea (64%), fatigue (52%), and injection-site reaction (52%). All CRS events were low grade (grade 1, 48%; grade 2, 20%), with most events occurring after the first full dose (C1D15). All CRS events resolved (median time to resolution, 2 d), and none led to epcoritamab discontinuation. No ICANS or clinical tumor lysis syndrome events occurred.
An immunophenotypic analysis revealed a sustained reduction in peripheral CD4+ T cells, with median cell count declining from 251 cells/µL at C1D1 to 167 cells/µL at C2D15 and remaining low up to C7D1. This CD4 lymphopenia, which may be attributed to bendamustine, was primarily grade 1 or 2 based on CTCAE v5.0 criteria and could be associated with an increased risk of infection. Conversely, at C2D15, CD8+ T cells expanded 2.5-fold from baseline and generally remained elevated up to C7D1, resulting in a reduced CD4:CD8 ratio. Excluding COVID-19, the infection rates are consistent with those seen in similar regimens.
Conclusions: Fixed-duration epcoritamab + BR showed deep and durable responses in 1L FL, with nearly all pts having a CR (96%) and most complete responders remaining in CR at 30 mo (87%), translating to favorable long-term outcomes (30-mo PFS, 83%; 30-mo OS, 96%). The safety profile was manageable, with no ICANS events and only low-grade, predictable CRS events, all of which resolved; however, the COVID-19 pandemic did impact study pts. These results compare favorably with BR alone and support further investigation of epcoritamab + BR in 1L FL and continued evaluation of epcoritamab as a core tx across non-Hodgkin lymphoma.
Disclosures: Falchi: Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; EvolveImmune: Consultancy; Genmab: Consultancy, Research Funding; Memorial Sloan Kettering Cancer Center: Current Employment; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech, Roche, Genmab, AbbVie, Innate, BeiGene: Research Funding; Genentech, Roche, Genmab, Abbvie, Sanofi, EvolveImmune: Honoraria; AbbVie, Genentech, ADC Therapeutics, Seagen, Ipsen: Membership on an entity's Board of Directors or advisory committees; Taylor Francis: Other: Journal Editor; Kaplan: Other: CME Presentation: Projects in Knowledge; Roche: Consultancy, Research Funding. Vitolo: AbbVie, Incyte, Janssen, Regeneron, Roche, Servier: Other: Lecture Fees; AbbVie, Bayer, Genmab, Gilead, Novartis: Membership on an entity's Board of Directors or advisory committees. Patah: AbbVie: Current Employment. Marek: Genmab: Current Employment. Morehouse: Genmab: Current Employment, Current equity holder in publicly-traded company. Steele: Janssen: Other: owns Janssen stock; Genmab: Current Employment, Other: owns Genmab stock; AbbVie: Other: owns AbbVie stock. Hao: Genmab: Current Employment. Hoehn: Genmab: Current Employment, Current equity holder in publicly-traded company. Linton: BeiGene: Consultancy, Research Funding; Celgene: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; Step Pharma: Research Funding; Regeneron: Research Funding; MorphoSys: Research Funding; MSD: Research Funding; Nurix: Research Funding; AstraZeneca: Research Funding; Janssen: Research Funding; Viracta: Research Funding; CellCentric: Research Funding; ADC Therapeutics: Research Funding; Roche: Consultancy, Research Funding; Kite/Gilead: Consultancy, Research Funding; BMS: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; AbbVie: Consultancy, Research Funding, Speakers Bureau; Genmab: Consultancy, Other: Member of the Epcoritamab Global Council, Research Funding.