Real-world outcomes with bispecific T-cell engagers in lymphoma worse than pivotal trials
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Key takeaways:
- Patients with relapsed or refractory large B-cell lymphoma who received epcoritamab or glofitamab in real-world settings experienced worse outcomes than observed in trials.
- Higher toxicity rates also occurred.
SAN DIEGO — Patients with relapsed or refractory large B-cell lymphoma who received epcoritamab or glofitamab in real-world settings achieved worse survival outcomes than those who received the agents in pivotal trials.
Immune effector cell-associated neurotoxicity syndrome (ICANS) and grade 3 or greater cytokine release syndrome also occurred at higher rates in real-world settings, data presented at ASH Annual Meeting and Exposition showed.
Background and methods
Epcoritamab-bysp (Epkinly; Genmab, AbbVie) and glofitamab-gxbm (Columvi, Genentech) are bispecific antibodies currently approved in the U.S. for the treatment of relapsed or refractory large B-cell lymphomas.
Results of pivotal trials showed high response rates and manageable toxicity profiles; however, limited data exist about outcomes of patients treated with either agent outside clinical trials.
Researchers conducted a retrospective study to assess the efficacy and safety of both agents for treatment of patients with relapsed or refractory large B-cell lymphomas in real-world settings.
The study included 209 patients (median age, 67 years; 62.2% men) with relapsed or refractory large B-cell lymphomas who received epcoritamab (n = 139) or glofitamab (n = 70) in 2023 or 2024.
The majority (74.2%) of patients in the analysis had diffuse large B-cell lymphoma.
Among 168 patients who underwent molecular testing, 34 (20.2%) had double/triple hit lymphoma. Most had Ann Arbor stage III to stage IV disease (78.9%) and an ECOG performance of 1 or lower (91%).
Patients had received a median three (range, 1-12) lines of treatment prior to receiving bispecific antibodies.
Most patients (60.3%) received prior chimeric antigen receptor T-cell therapy, while 10% underwent prior autologous hematopoietic stem cell transplantation.
Investigators used medical records to determine efficacy outcomes, including overall response rate, CR, PR, PFS and OS. CRS and ICANS served as key safety outcomes.
Results, next steps
The analysis included 172 patients evaluable for response.
Researchers reported a best ORR of 50.6%, with 41 patients (23.8%) achieving complete response and 46 (26.7%) achieving partial response. Ten (5.8%) exhibited stable disease and 75 (43.6%) developed progressive disease.
Results showed a 49% ORR and 23% complete response rate among patients who received epcoritamab, and a 53% ORR and 25% complete response rate among those who received glofitamab had an ORR of 53% and a CR rate of 25%.
Among all evaluable patients, with median follow-up of 5 months, researchers reported median PFS of 2.7 months (95% CI, 2–3.9) and median OS of 7.2 months (95% CI, 6.1 to not reached). They reported estimated 6-month PFS of 35% (95% CI, 29%-43%) and estimated 6-month OS of 59% (95% CI, 52%-67%).
Patients who relapsed following CAR-T had median PFS of 2.5 months (95% CI, 1.8-4.7) and median OS of 7.8 months (95% CI, 6.2 to not reached).
Patients without detectable CD20 expression via immunohistochemistry or flow cytometry prior to bispecific antibody therapy had inferior outcomes compared with patients who had detectable CD20 (median PFS, 1.1 months vs. 3.4 months; median OS, 1.3 months vs. 13 months).
Eighty-two patients (39.2%) developed any-grade CRS, with a higher rate among those treated with epcoritamab than glofitamab (51.1% vs. 28.6%). Nine patients (4.3%) developed grade 3 or higher CRS; all had received epcoritamab.
Twenty-four patients (11.5%) developed ICANS, with a higher rate among those treated with epcoritamab than glofitamab (13.7% vs. 7.1%). Six patients (2.9%) developed grade 3 or higher ICANS; five had received epcoritamab.
One patient died of CRS and two died of ICANS.
A total of 122 patients (58.4%) discontinued therapy, with discontinuation occurring after a median three cycles (range, 0-48). Ninety-one (74.6%) discontinued due to disease progression and 31 (25.4%) did so due to adverse events (infection, n = 15; ICANS, n = 3, CRS, n = 2; other reasons, n = 11).
“In this heavily pretreated group with adverse disease features and high rate of CAR-T exposure, the response rates, PFS and OS following [bispecific antibody] therapy were lower compared [with] pivotal trials,” researchers wrote. “Future efforts to improve outcomes may include intensified dose escalation protocols to more rapidly achieve disease control, combination therapies, and characterization of clinicopathologic factors that predict response to [bispecific antibodies] to identify subgroups of patients who can derive maximal benefit from these agents.”
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Brooks TR, et al. Abstract 111. Presented at: ASH Annual Meeting and Exhibition; Dec. 7-10, 2024; San Diego.
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