Anti-BCMA CAR-T Cell Therapy in Relapsed/Refractory Multiple Myeloma Patients With Extramedullary Disease: A Single Center Analysis of Two Clinical Trials

Front Immunol. 2021 Oct 29:12:755866. doi: 10.3389/fimmu.2021.755866. eCollection 2021.

Abstract

Background: The prognosis of relapsed/refractory multiple myeloma (RRMM) patients with the extramedullary disease was significantly poor. Extramedullary multiple myeloma (EMM) patients gained limited benefits from traditional drugs. Anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy seems to be a promising approach to treat RRMM patients. However, very few clinical studies are designed for EMM. Our study aimed to compare and assess the safety, efficacy, and pharmacokinetics of anti-BCMA CAR-T cell therapy in EMM and non-EMM.

Methods: The results from published anti-BCMA CAR-T clinical trials, in which raw data of EMM patients were available, were reviewed and summarized. Two trials conducted in our clinical centers were analyzed and presented with detailed data.

Results: According to published anti-BCMA CAR-T clinical trials, the ORR of EMM ranged from 57% to 100%, with the complete remission (CR) rate of 29% to 60%. Between February 22, 2017, and September 26, 2019, a total of 61 subjects (EMM 25; non-EMM 36) received anti-BCMA CAR-T cell infusion. The data-cutoff date was April 1, 2021. There were no statistical differences between EMM and non-EMM groups in adverse events (AEs), including cytokine release syndrome (CRS). The most common AEs of grade ≥ 3 in both groups were hematologic toxicities. There was no significant difference in the objective response rate (ORR) and ≥ complete remission (CR) rate between both groups. However, the ≥ CR rate of the EMM group was lower than the non-EMM group receiving the fully human anti-BCMA CAR-T cell therapy (p = 0.026). The median progression-free survival (PFS) for EMM and the non-EMM group was 121 days and 361 days, respectively (p = 0.001). The median overall survival (OS) for EMM and the non-EMM group was 248 days and 1024 days, respectively (p = 0.005). The Cmax and AUC0-28d for EMM group were lower than non-EMM group (Cmax, p = 0.016; AUC0-28d, p = 0.016). Extramedullary disease was an independent prognostic risk factor for PFS (hazard ratio, 2.576; 95% CI, 1.343 to 4.941; p = 0.004) and OS (hazard ratio, 2.312; 95% CI, 1.165 to 4.592; p = 0.017) in RRMM patients receiving anti-BCMA CAR-T cell therapy.

Conclusions: Based on our results, EMM patients could benefit from the two anti-BCMA CAR products, although they had a shorter PFS and OS compared with non-EMM patients.

Clinical trial registration: http://www.chictr.org.cn, identifier ChiCTR-OPC-16009113 and ChiCTR1800018137.

Keywords: BCMA (TNFRSF17); car-t; extramedullary; multiple myeloma; refractory; relapsed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • B-Cell Maturation Antigen / antagonists & inhibitors*
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Female
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Male
  • Middle Aged
  • Multiple Myeloma / mortality
  • Multiple Myeloma / therapy*
  • Neoplasm Recurrence, Local / therapy
  • Progression-Free Survival
  • Receptors, Chimeric Antigen
  • Retrospective Studies
  • Treatment Outcome*

Substances

  • B-Cell Maturation Antigen
  • Receptors, Chimeric Antigen
  • TNFRSF17 protein, human

Associated data

  • ChiCTR/ChiCTR-OPC-16009113
  • ChiCTR/ChiCTR1800018137