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Sequential Bispecific Antibodies and CAR-T Use Is a Safe and Effective Strategy in Relapsed Refractory Hematologic Malignancies

Year: 2026

Type: article

Abstract: Introduction Chimeric antigen receptor T cell (CAR-T) therapy has transformed the management of relapsed/refractory (R/R) hematologic malignancies. Prolonged use of bispecific antibodies (BsAb) provides effective T cell based immunotherapy but may induce T cell exhaustion, cross resistance, and increased toxicity, potentially impacting subsequent CAR-T efficacy. We retrospectively evaluated outcomes and toxicity in patients receiving sequential BsAb and CAR-T. Objectives Evaluate outcomes and toxicity of sequential BsAb and CAR-T for R/R hematologic malignancies. Methods We retrospectively reviewed 10 patients with R/R hematologic malignancies who received BsAb before CAR-T (2023–7/2025). Data included prior therapy, BsAb use, response, toxicity, CAR-T manufacturing, timing, outcomes, and complications (cytokine release syndrome [CRS], immune effector cell associated neurotoxicity syndrome [ICANS], infections, hospitalizations, ICU admissions). Descriptive statistics were applied; progression free survival (PFS) and overall survival (OS) were estimated by Kaplan Meier. Study was approved by Institutional Review Board. Results Median age was 62.5 years (range: 46–75); 80% male. Diagnoses included multiple myeloma (20%), B-cell non-Hodgkin lymphoma (50%), and acute lymphoblastic leukemia (30%). BsAb was initiated for disease stabilization (60%) or progressive disease (PD) (40%) using talquetamab (20%), mosunetuzumab (20%), blinatumomab (30%), and glofitamab (30%) over a median of 58 days. Overall response rate (ORR) was 70%, (complete response [CR] 20%). 30 % had PD. BsAb was last regimen prior to CAR-T in 70%. CAR-T manufacturing was successful in all; 70% initiated BsAb after leukapheresis (median interval 21 days, range 0–148), 30% before leukapheresis (median interval 48 days, range 2–114). Median leukapheresis to CAR-T interval was 86 days (range 20-414). CAR-T included axicabtagene ciloleucel (40%), brexucabtagene autoleucel (40%), and ciltacabtagene autoleucel (20%). One patient died on day 14 post CAR-T (intracranial hemorrhage) and was excluded from response analysis. Among nine evaluable patients, six-month ORR was 89%, (CR 44%). 11% had PD. Kaplan Meier curves show most events within first 3–4 months post CAR-T, followed by a plateau. Estimated 12-month OS and PFS were 70%; with medians not reached. Outcomes suggest early risk followed by durable responses, though limited by small sample size (Figure 1, 2). Incidence of CRS and ICANS with BsAb and CAR-T is mentioned in table 2 & 3. Ninety percent were hospitalized within 100 days post CAR-T (CRS/ICANS 56%, infections 44%) including 2 ICU admissions. Conclusion Sequential BsAb and CAR-T therapy was feasible, with high manufacturing success, promising early responses, and manageable toxicity. Notably, no grade ≥3 CRS occurred post CAR-T per ASTCT criteria.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.jtct.2025.12.280