BAFFR-CAR T cells (PMB-CT01) show promising safety and anti-leukemia efficacy in relapsed/refractory B-cell ALL patients after CD19-targeted therapy failure, including CD19-negative disease

作者：Ibrahim Taha Aldoss, Xiuli Wang, Lu Chen, Joo Young Song, Karamjeet Sandhu, Alan Macias, Neguine Sanani, Baishakhi Barva, Min Guan, Ruby Espinosa, Sandrine Puverel, Qing Liu-Michael, Hazel Cheng, Guido Marcucci, Elizabeth E. Budde, Larry W. Kwak, Stephen J. Forman · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-813 · 被引用次数：3 · 研究领域：CAR-T cell therapy research、Acute Lymphoblastic Leukemia research、CRISPR and Genetic Engineering

Abstract Introduction: Immunotherapies targeting CD19, such as blinatumomab and CAR T cells, have shown remarkable efficacy in relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). However, many adults fail to respond to blinatumomab, and while CD19 CAR T cells induce high initial response rates, relapse occurs in up to 50% of patients. Patients (pts) who fail CD19-targeted immunotherapies have dismal outcomes with limited therapeutic options. Tumor escape through epitope loss represents a major challenge, especially as these therapies move into earlier treatment lines. To address the need for novel targeted therapies, we have developed CAR T cells against the B-cell activating factor receptor (BAFF-R), a B-cell marker functionally expressed in B-ALL, including CD19-negative relapses (Qin et al., Sci Transl Med. 2019). Given the essential role of BAFF-R in B-cell function and survival, the ability of malignant cells to evade therapy by antigen downregulation may be limited. Methods: This is a phase 1 dose-escalation trial of BAFFR-CAR T cells (PMB-CT01) in pts with r/r B-ALL who are ineligible for, or who failed prior CD19-targeted therapy (NCT04690595). Dose escalation follows a modified 3+3 design with 4 dose levels (DL). DL-1 (de-escalation) and DL1 (starting dose) consist in infusion with 20M and 50M CAR T cells, respectively, after lymphodepletion (LD) with cyclophosphamide only. DL2, DL3, and DL4 consist in infusion with 50M, 200M, and 600M cells, respe...