Bispecific antibodies as bridging to BCMA CAR-T cell therapy for relapsed/refractory multiple myeloma.

IF 11.5 Q1 HEMATOLOGY Blood Cancer Discovery Pub Date : 2024-10-23 DOI:10.1158/2643-3230.BCD-24-0118

David Fandrei, Sabine Seiffert, Michael Rade, Susanne Rieprecht, Nico Gagelmann, Patrick Born, Thomas Wiemers, Heike Weidner, Markus Kreuz, Tamara Schassberger, Jannik Kossmann, Marlene Mangold, Daniel Furst, Luise Fischer, Ronny Baber, Simone Heyn, Song Yau Wang, Enrica Bach, Sandra Hoffmann, Klaus H Metzeler, Marco Herlling, Madlen Jentzsch, Georg-Nikolaus Franke, Ulrike Kohl, Maik Friedrich, Andreas Boldt, Kristin Reiche, Uwe Platzbecker, Vladan Vucinic, Maximilian Merz

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Abstract

Establishing a strategy for sequencing of T cell redirecting therapies for relapsed/refractory multiple myeloma (RRMM) is a pressing clinical need. We longitudinally tracked the clinical and immunological impact of bispecific T cell engaging antibodies (BsAb) as bridging therapy (BT) to subsequent BCMA-directed CAR-T cell therapies in 52 RRMM patients. BsAbs were a potent and safe option for BT, achieving the highest overall response rate (100%) to BT compared to chemotherapy, anti-CD38 or anti-SLAMF7 antibody based regimens (46%). We observed early CD4+CAR+ and delayed CD8+CAR+ T cell expansion in patients receiving BsAb as BT. In vitro cytotoxicity of CAR-T cells was comparable amongst BT options. Single-cell analyses revealed increased clonality in the CD4+ and CD8+ T cell compartments in patients with previous exposure to BsAbs at leukapheresis and on day 30 after CAR-T infusion. This study demonstrates the feasibility and efficacy of BT with BsAbs for CAR-T cell therapy in RRMM.

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双特异性抗体是治疗复发/难治性多发性骨髓瘤的 BCMA CAR-T 细胞疗法的桥梁。

为复发/难治性多发性骨髓瘤（RRMM）的T细胞重定向疗法制定排序策略是一项迫切的临床需求。我们对52例RRMM患者进行了纵向追踪，研究了双特异性T细胞吸引抗体（BsAb）作为桥接疗法（BT）对后续BCMA导向CAR-T细胞疗法的临床和免疫学影响。与化疗、抗CD38或抗SLAMF7抗体疗法（46%）相比，双特异性抗体是一种有效而安全的桥接疗法，其总反应率（100%）最高。我们在接受 BsAb 作为 BT 的患者中观察到早期 CD4+CAR+ 和延迟 CD8+CAR+ T 细胞扩增。各种 BT 方案的 CAR-T 细胞体外细胞毒性相当。单细胞分析显示，在白细胞清除时和输注 CAR-T 后第 30 天，曾接触过 BsAb 的患者 CD4+ 和 CD8+ T 细胞区的克隆性增加。这项研究证明了在 RRMM 的 CAR-T 细胞疗法中使用 BsAbs 进行 BT 的可行性和有效性。

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来源期刊

Blood Cancer Discovery Multiple-

CiteScore

12.70

自引率

1.80%

发文量

139

期刊介绍： The journal Blood Cancer Discovery publishes high-quality Research Articles and Briefs that focus on major advances in basic, translational, and clinical research of leukemia, lymphoma, myeloma, and associated diseases. The topics covered include molecular and cellular features of pathogenesis, therapy response and relapse, transcriptional circuits, stem cells, differentiation, microenvironment, metabolism, immunity, mutagenesis, and clonal evolution. These subjects are investigated in both animal disease models and high-dimensional clinical data landscapes. The journal also welcomes submissions on new pharmacological, biological, and living cell therapies, as well as new diagnostic tools. They are interested in prognostic, diagnostic, and pharmacodynamic biomarkers, and computational and machine learning approaches to personalized medicine. The scope of submissions ranges from preclinical proof of concept to clinical trials and real-world evidence. Blood Cancer Discovery serves as a forum for diverse ideas that shape future research directions in hematooncology. In addition to Research Articles and Briefs, the journal also publishes Reviews, Perspectives, and Commentaries on topics of broad interest in the field.