Risk factors associated with durable progression-free survival in relapsed or refractory multiple myeloma patients treated with anti-BCMA CAR-T cell therapy.

Purpose 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. Experimental design 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. Results Sixty patients (98.4%) experienced cytokine release syndrome (CRS), including 33, 23, and four cases of CRS grades 1-2, 3, and 4, respectively. 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. 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 CR 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). Conclusions 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.