CAR‐T cell therapy targeting B cell maturation antigen is effective for relapsed/refractory multiple myeloma, including cases with poor performance status

Abstract In this open‐label, single‐arm, phase I/II clinical trial, we evaluated the efficacy of anti‐B cell maturation antigen (BCMA) chimeric antigen receptor (CAR)‐T cell (HDS269B) therapy in 49 relapsed/refractory multiple myeloma (RRMM) patients, including 20 with Eastern Cooperative Oncology Group (ECOG) grade 3–4. After HDS269B infusion (9 × 10 6 CAR + cells/kg), 17 patients (34.69%, 11 ECOG 0–2, 6 ECOG 3–4) developed cytokine release syndrome grade 1–2: 14 patients (28.57%); grade 3: 3 patients (6.12%). The objective response rate (ORR) was 77%, with a complete response (CR) achieved in 47%. Ongoing response >12 months occurred in 15 patients, and was extended beyond 38 months in one patient. The median progression‐free survival (PFS) and overall survival (OS) were 10 months (95% CI 5.3–14.7) and 29 months (95% CI 10.0–48.0), respectively. The PFS (12 months) and OS (18 months) rates were 41.64% and 62.76%, respectively. In patients with ECOG 0–2 and 3–4, ORR was 79.31% (23/29) and 75.0% (15/20) and PFS were 15 months (95% CI 5.4–24.6) and 4 months (95% CI 0–11.7), respectively. OS was not reached in ECOG 0–2 patients, but was 10.5 months (95% CI 0–22) in ECOG 3–4 patients. Single‐cell sequencing indicated that treatment efficacy might be related to mTORC1 signaling. Thus, HDS269B therapy is safe and effective for RRMM patients, even those with ECOG 3–4.