Factors Associated with Durable Progression-Free Survival in Relapsed or Refractory Multiple Myeloma Patients after Potent Anti-BCMA CAR-T Cell Therapy

Abstract

Background: B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) cell therapy results in high remission rates in patients with relapsed/refractory (R/R) multiple myeloma (MM). However, the factors associated with prognosis following CAR-T cell therapy are unknown. Methods: Between July 1, 2018, and July 31, 2020, 61 patients with R/R MM received anti-BCMA CAR-T cell therapy (Chictr.org number, ChiCTR1800017404). Stepwise multivariate Cox regression and competing risk analyses were conducted to identify poor prognosis-associated risk factors. Findings: Sixty patients (98·4%) experienced cytokine release syndrome (CRS), including seven, 26, 23, and four cases of CRS grades 1, 2, 3, and 4, respectively. Only five cases of reversible neurological toxicities occurred. The objective response rate (ORR) was 98·3%, and the complete response (CR) rate was 70·3%. With a median follow-up period of 21·1 months, the one-year overall survival (OS) and progression-free survival (PFS) rates were 78·0% and 50·2%, respectively. The median PFS was 12·7 months. Multivariate Cox modeling revealed that poor PFS was associated with extramedullary disease (hazard ratio (HR)=2 ·59, 95% confidence interval (95%CI)=1·29–5·21, P =0·008), light chain MM (HR=2·53, 95%CI=1·03–5·97, P =0·035), high-risk cytogenetics (HR=2·80, 95%CI=1·27–6·14, P =0·01), and prior treatment with >3 therapeutic lines (HR=3·14, 95%CI=1·34–7·34, P =0·008). Among the 41 complete remission cases, competing risk analyses demonstrated higher relapse predispositions in those with extramedullary disease (HR=4·51, 95%CI=1·86 –10·9, P =0·001), light chain MM (HR=4·89, 95%CI=1·52 –15·7, P =0·008), or high-risk cytogenetics (HR=5·09, 95%CI=1·63 –15·9, P =0·005). Furthermore, patients with more risk factors had worse outcomes. Interpretation: Anti-BCMA CAR-T cell therapy is safe and effective for R/R MM. For patients with high-risk factors, improvements to extend remission and more specific individualized therapies are needed. Funding: Natural Science Foundation of China, Key Project of Science and Technology Department of Zhejiang Province, Key R&D Project of Zhejiang Science and Technology Department, National Key Basic Research Program of China, National Natural Science Foundation of China. Declaration of Interest: AHC is a founding member of Shanghai YaKe Biotechnology Ltd., a biotechnology company focused on research and development of tumor cellular immunotherapy. The remaining authors declare no conflict of interest. Ethical Approval: The protocol was approved by the 1st Affiliated Hospital, School of Medicine, Zhejiang University Institutional Review Board. All patients provided written informed consent to participate in the study.