<scp>CAR‐T</scp> cell therapy targeting B cell maturation antigen is effective for relapsed/refractory multiple myeloma, including cases with poor performance status
Juan Du, Runhong Wei, Songfu Jiang, Hua Jiang, Lu Li, Wanting Qiang, Haiyan He, Lin Shi, Qiuling Ma, Kang Yu, Xiaoyuan Zhang, Hanyi Ding, Xuedong Sun, Xiang Fang, Lin Zhu, Cheng Zhi, Weijun Fu
Abstract
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.