Efficacy and safety of chimeric antigen receptor T cells targeting BCMA and GPRC5D in relapsed or refractory multiple myeloma

Front Immunol. 2024 Dec 23:15:1466443. doi: 10.3389/fimmu.2024.1466443. eCollection 2024.

Abstract

Background: Clinical studies have demonstrated the high efficacy of using chimeric antigen receptor (CAR)-T cells targeting B-cell maturation antigen (BCMA) and orphan G protein-coupled receptor, class C group 5 member D (GPRC5D) to treat relapsed or refractory multiple myeloma (RRMM). In this study, we compared the efficacy and safety of BCMA CAR-T-cell therapy (BCMA CAR-T) and GPRC5D CAR T-cell therapy (GPRC5D CAR-T) in patients with RRMM.

Methods: We retrieved and included eligible clinical trials of BCMA or GPRC5D CAR-T for RRMM patients. The primary outcomes for efficacy were overall response rate (ORR), complete response rate (CRR), minimal residual disease (MRD) negativity, and relapse rate. The primary outcomes for safety were cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).

Results: We incorporated 18 early-phase, single-arm clinical trials, which included 503 and 133 patients receiving BCMA CAR-T and GPRC5D CAR-T, respectively. For the GPRC5D CAR-T cohort, the estimated ORR, CRR, MRD negativity rate, and relapse rate were found to be 89.8% [95% confidence interval (CI), 82.8%-96.9%], 50.5% (95% CI, 38.0%-62.9%), 78.8% (95% CI, 53.0%-100%), and 26.0% (95% CI, 7.4%-44.6%), respectively. In the BCMA CAR-T group, the ORR was 76.3% (95% CI, 67.9%-84.7%), the CRR was 34.3% (95% CI, 25.9%-42.7%), the MRD negativity rate was 76.5% (95% CI, 63.1%-90.0%), and the recurrence rate was 57.3% (95% CI, 47.7%-66.9%). These values were significantly lower than those observed in the GPRC5D CAR-T cohort. Both BCMA and GPRC5D CAR-T demonstrated acceptable safety. The estimated incidence of BCMA CAR-T resulting in grade 3-5 CRS and ICANS was only 5.4% (95% CI, 2.0%-10.4%) and 3.3% (95% CI, 0.6%-8.0%), respectively. The estimated incidence of GPRC5D CAR-T resulting in grade 3-5 CRS and ICANS was only 1.6% (95% CI, 0.0%-6.5%) and 2.7% (95% CI, 0.7%-6.2%), respectively.

Conclusion: GPRC5D CAR-T potentially demonstrates enhanced effectiveness relative to BCMA CAR-T in treating patients with RRMM. Therefore, GPRC5D CAR-T can be regarded as the preferred therapeutic option for RRMM, particularly among patients who have undergone relapse subsequent to BCMA CAR-T treatment.

Keywords: B-cell maturation antigen; G protein-coupled receptor; car-T; class C group 5 member D; relapsed or refractory multiple myeloma.

Publication types

  • Systematic Review

MeSH terms

  • Aged
  • B-Cell Maturation Antigen* / immunology
  • Female
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Immunotherapy, Adoptive* / methods
  • Male
  • Middle Aged
  • Multiple Myeloma* / immunology
  • Multiple Myeloma* / therapy
  • Neoplasm Recurrence, Local / immunology
  • Receptors, Chimeric Antigen* / genetics
  • Receptors, Chimeric Antigen* / immunology
  • Receptors, G-Protein-Coupled* / immunology
  • Treatment Outcome

Substances

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

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (grant number 82160519); the Natural Science Foundation of Guizhou Province (grant number QianKeHe Basics - ZK(2023) Key 042, Qiankehe Cooperation Platform talents(2021) Postdoctoral Station - 007); the Research Project of Education Department of Guizhou Province (grant number QianJiaoJi (2023)037); the Subject Excellent Reserve Talent Project (grant number gyfyxkrc-2023-14). The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.