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 × 106 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.

• Authors: 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, Fang Xiang, Lin Zhu, Zhi Cheng, Weijun Fu
• Journal: American journal of hematology (Am J Hematol) Vol. 97 Issue 7 Pg. 933-941 (07 2022) ISSN: 1096-8652 [Electronic] United States
• PMID: 35488407 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 Wiley Periodicals LLC.

Chemical References

• B-Cell Maturation Antigen
• Receptors, Chimeric Antigen

Topics

• B-Cell Maturation Antigen
• Cell- and Tissue-Based Therapy
• Humans
• Immunotherapy, Adoptive (adverse effects)
• Lymphoma, Follicular
• Multiple Myeloma (drug therapy)
• Receptors, Chimeric Antigen (therapeutic use)