According to results from a retrospective study, the bispecific antibodies epcoritamab and glofitamab demonstrate worse outcomes in the real-world setting compared to their pivotal trials among patients with relapsed or refractory large b-cell lymphomas (LBCLs). 

These results were presented by Taylor Brooks, MD, Taussig Cancer Institute, Cleveland, Ohio, at the 2024 American Society of Hematology (ASH) Annual Meeting in San Diego, California. 

In this multicenter, retrospective study, researchers collected baseline characteristic and outcome data from 209 patients with patients with relapsed or refractory LBCLs who received either epcoritamab (n = 139) or glofitamab (n = 70). There were 126 patients who underwent chimeric antigen receptor (CAR)-T cell therapy previously and 21 who underwent hematopoietic progenitor cell transplant previously. Of 106 biopsies assessed for CD20 expression, 84.9% were CD20-positive. Primary end points included overall response rate (ORR), complete and partial response rate, progression-free survival (PFS), and overall survival (OS). A key secondary end point was safety. 

At analysis, the best ORR was 50.6% with 41 complete responses and 46 partial responses. There were 10 patients with stable disease and 75 with progressive disease. The ORR was 49% with epcoritamab and 53% with glofitamab. The complete response rate was 23% with epcoritamab and 25% with glofitamab. At a median follow-up of 5 months, the median PFS was 2.7 months and the median OS was 7.2 months. The estimated 6-month PFS rate was 35% and the estimated 6-month OS rate was 59%. Among patients who relapsed after CAR-T cell therapy, the median PFS was 2.5 months and the median OS was 7.8 months. Among patients without detectable CD20 expression prior to bispecific antibody treatment, the median PFS was 1.1 months and 3.4 months (P = < .001), and the median OS was 1.3 months and 13 months (P <. 001), respectively. 

Any grade cytokine release syndrome (CRS) was observed in 82 patients (51.1% of patients who received epcoritamab and 28.6% of those who received glofitamab). Grade ≥3 CRS was observed in 9 patients (all treated with epcoritamab). Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 24 patients, (13.7% of patients who received epcoritamab and 7.1% of those who received glofitamab). Grade ≥3 ICANS was observed in 6 patients, 5 of whom received epcoritamab. 

After a median of 3 cycles, 58.4% of patients discontinued treatment due to disease progression (74.6%) and adverse events (25.4%). The most common adverse events that led to treatment discontinuation included infection (n = 15), ICANS (n = 3), CRS (n = 2), and other reasons (n = 11). Three deaths occurred, 2 due to ICANS and 1 to CRS. 

Dr Brooks et al concluded, “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 to pivotal trials…[and] poor outcomes were observed for those without detectable CD20.” To improve outcomes in the future, study authors suggested “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.” 

Source: 

Brooks TR, Zabor EC, Bedlu YB et al. Real-world outcomes with bispecific t-cell engagers (REALBiTE) for relapsed or refractory large b-cell lymphoma: A multi-center, retrospective cohort study. Presented at the 2024 American Society of Hematology (ASH) Annual Meeting. December 7-10, 2024; San Diego, CA. Abstract #111