Efficacy and safety of CD3×CD20 bispecific antibodies in Richter transformation: A systematic review of prospective trials and comparative analysis.

Abstract

e19095 Background: Richter transformation (RT), the progression of chronic lymphocytic leukemia to aggressive diffuse large B-cell lymphoma, carries poor outcomes. Chemoimmunotherapy (CIT), including R-CHOP, remains commonly used in the frontline setting, while CD19-directed CAR T-cell therapy is used mainly in relapsed/refractory (R/R) disease but is limited by toxicity and access. CD3×CD20-targeting bispecific antibodies (BsAbs) are off-the-shelf immunotherapies with emerging prospective data in RT. We systematically evaluated the efficacy and safety of BsAbs across treatment lines. Methods: We did a systematic search on PubMed, Google Scholar, and ClinicalTrials.gov. Updated studies of four trials met the inclusion criteria. Outcomes were stratified by line of therapy (first-line [1L] vs relapsed/refractory [R/R]) and regimen (monotherapy vs combination). Primary endpoints were overall response rate (ORR) and complete response (CR) per Lugano 2014 criteria. Cytokine release syndrome (CRS) was graded per ASTCT criteria. Results: A total of 138 patients were evaluated (97 monotherapy, 41 combination). In the 1L setting (n=21), epcoritamab monotherapy achieved an ORR of 57% and CR rate of 52%, with an mOS of 27.5 months, more than doubling historical CIT (R-CHOP) survival (<12 months). In R/R RT, mosunetuzumab (n=20) and glofitamab (n=11) demonstrated ORRs of 40% and 63.6% with CR rates of 20% and 45.5%, respectively. The BLINART study with Blinatumomab (n=25) reported an ORR of 46% and CR of 20%. Combination regimens (n=41) showed favorable responses similar to those reported with CD19-directed CAR T-cell therapy in multicenter registries, though cross-trial comparisons are limited: epcoritamab plus lenalidomide achieved a CR rate of 73%, and epcoritamab plus R-CHOP achieved a CR of 60%. Grade ≥3 CRS occurred in <9% of patients, lower than rates reported with CAR T-cell therapy (16%). Neutropenia was the most common grade ≥3 adverse event. Conclusions: CD3×CD20 bispecific antibodies demonstrate meaningful clinical activity in RT, with signals of improved frontline survival versus historical CIT and favorable efficacy and safety across R/R settings. More data from clinical trials is needed to establish clear superiority. Prospective CD3×CD20 BsAb trials in RT and comparison with R-CHOP and CAR T cell therapy. Trial / Regimen Population N ORR (%) CR (%) mOS Gr ≥3 CRS Epcoritamab + Lena R/R 11 82.0% 73.0% NR 9.0% Epcoritamab + R-CHOP R/R 30 73.0% 60.0% 16.4 mo 3.0% Epcoritamab Mono 1L 21 57.1% 52.0% 27.5 mo 7.0% Glofitamab Mono R/R 11 63.6% 45.5% NR 0.0% Mosunetuzumab Mono R/R 20 38.1% 29.0% 9.8 mo 7.0% Epcoritamab Mono R/R 20 40.0% 20.0% 11.4 mo 5.0% Blinatumomab (Seq) R/R 25 36.0% 20.0% NR 8.0% CIBMTR (CAR-T Ref) R/R 140 — — 46.6% (2-yr OS) — Kittai et al. (CAR-T Ref) 1L 69 63.0% 46.0% 8.5 mo 16.0% R-CHOP (CIT Ref) 1L — 40–60% 20.0% 6–12 mo 0.0%