Risk Factors Associated with Durable Progression-Free Survival in Patients with Relapsed or Refractory Multiple Myeloma Treated with Anti-BCMA CAR T-cell Therapy

Abstract

Purpose: B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy results in high remission rates in patients with relapsed/refractory (R/R) multiple myeloma. However, the factors associated with prognosis following CAR T-cell therapy are unknown.

Patients and methods: Between July 1, 2018 and July 31, 2020, 61 patients with R/R multiple myeloma received anti-BCMA CAR T-cell therapy (Chictr.org number, ChiCTR1800017404). Step-wise 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 4 cases of CRS grades 1 to 2, 3, and 4, respectively. The objective response rate (ORR) was 98.3%, and the complete remission (CR) rate was 70.3%. With a median follow-up period of 21.1 months, the 1-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 [HR = 2.59, 95% confidence interval (95% CI) = 1.29-5.21, P = 0.008], light chain multiple myeloma (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 more than 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 multiple myeloma (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 multiple myeloma. For patients with high-risk factors, improvements to extend remission and more specific individualized therapies are needed.

Figure 1.

CONSORT diagram.

Figure 2.

Tumor response and subgroup analysis of response. A, Follow-up of 61 patients treated with BCMA CAR T cells. B, The rate of CR according to characteristics at baseline and during treatment. DS, Durie-Salmon.

Figure 3.

PFS and subgroup analysis. A, The PFS in all patients. B, The PFS in patients with or without extramedullary disease. C, The PFS in patients with or without high-risk cytogenetics (TP53 mutation, del17p, or 1q21 gain or amplification). D, The PFS in patients with light chain or other types. E, The PFS in patients with light chain and other types. F, The PFS in patients with different number of independent factors.

Figure 4.

CIR and subgroup analysis among 41 patients who achieved CR. A, The CIR in all patients. B, The CIR in patients with or without extramedullary disease. C, The CIR in patients with or without high-risk cytogenetics (TP53 mutation, del17p, or 1q21 gain or amplification). D, The CIR in patients with light chain or other types. E, The CIR in patients with different number of independent factors.