According to a retrospective, real-world study, while bispecific antibody therapy demonstrated efficacy among patients with relapsed/refractory large B-cell lymphoma (LBCL) after failure on CAR-T cell therapy, that efficacy was significantly reduced among patients who experienced CAR-T cell failure within the first 3 months.

These results will be presented by Evgenii Shumilov, MD, University Hospital Muenster, Germany, at the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition in San Diego, California.

CD20XCD3 T-cell–engaging bispecific antibodies have shown promise for patients with LBCL who are relapsed or refractory following CD19 CAR-T cell therapy. While glofitamab and epcoritamab have demonstrated efficacy in trials, Dr Shumilov and coauthors noted, “data on the efficacy and safety of [bispecific antibodies] post–CAR-Ts in the real-world setting are scarce.”

This retrospective, multicenter, multinational analysis enrolled 85 patients with relapsed/refractory large B-cell lymphoma who had experienced CAR-T cell failure and were treated with bispecific antibodies. Patients had diffuse large B-cell lymphoma (DLBCL, n= 55), transformed indolent lymphoma (n = 18), high grade B-cell lymphoma (n = 10), primary mediastinal B-cell lymphoma (n = 1), and T-cell/hisiocyte-rich large B-cell lymphoma (n = 1). Efficacy and feasibility of bispecific antibodies in the real-world setting was assessed depending on the timing of CAR-T cell failure: early (within the first 3 months, n = 43); intermediate (4 to 6 months, n = 24) or late (>6 months, n = 18). Additionally, there were 51 patients who received bispecific antibody therapy immediately upon failure of the CAR-T cell therapy, and 34 who had a median of 1 therapy between CAR-T cell failure and bispecific antibody therapy. Efficacy was evaluated through objective response rate (ORR), complete response, partial response, median progression-free survival (PFS), and median overall survival (OS).

There were 42% of patients who responded to bispecific antibody therapy, 23% achieved a complete response and 19% achieved a partial response. The ORR among patients who received bispecific antibodies immediately was 47% and among those who had ≥1 therapy between was 35%. The ORR also differed among the CAR-T cell failure timing cohorts: 30% in the early failure group, 50% in the intermediate failure group, and 61% in the late failure group. The median PFS was 3.27 months and the median OS was 6.83 months. The estimated median PFS was significantly improved for those who immediately received bispecific antibodies compared to those had ≥1 therapy in between (4.37 months vs 2.48 months; P = .026). The median OS was not significantly different between these 2 groups (7.73 months vs 5.10 months; P = .100). The median PFS and median OS differed significantly within the CAR-T failure timing cohorts (P ≤ .004). The early group had a median PFS of 2.13 months and a median OS of 4.10 months. The intermediate group was 3.73 months and 7.73 months, respectively. The late group was 10.46 months and not reached, respectively. Upon multivariate analysis, the strongest predictors of survival after starting bispecific antibody therapy were sensitivity to last treatment prior to bispecific antibodies, timing of CAR-T cell failure, additional therapies between CAR-T cell and bispecific antibody therapies, and LDH levels prior to application of bispecific antibodies considered as continuous variable.

There were 31% of patients who experienced cytokine release syndrome (CRS), with 3% of events documented as grade 3/4. There was 1 patients who experienced a severe immune effector cell-associated neurotoxicity syndrome. Infections were reported in 36% of patients, 11% with grade 3, and 3 patients with grade 5. All of those grade 5 events were associated with COVID-19.

Dr Shumilov et al concluded that bispecific antibodies “show efficacy and manageable safety profiles” among patients with relapsed/refractory LBCL after failure on CAR-T cell therapy in the real-world setting. Study authors noted, the efficacy of bispecific antibody therapy “is significantly impaired in early CAR-T refractory [patients] underscoring the necessity of novel therapeutic approaches” among these patients.

Source:

Shumilov E, Wurm-Kuczera R, Vucinic V, et al. Time of CAR-T failure is a strong predictor of outcome for bispecific antibody therapy in relapsed/refractory large B-cell lymphoma. Presented at 2024 ASH Annual Meeting & Exposition. Dec 7-10, 2024; San Diego, CA. Abstract: 114