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<p>Relapse following B-cell maturation antigen (BCMA)-directed therapies represents a critical challenge in relapsed/refractory multiple myeloma (R/R MM). We performed a systematic review and meta-analysis of 34 studies (<i>n</i> = 1280) published between 2020 and 2025 to evaluate salvage CAR-T versus engineered antibody therapies post-BCMA exposure. The pooled overall response rate (ORR) was 60%. CAR-T therapy achieved significantly superior ORR compared to antibody-based approaches (77% vs 52%; <i>p</i> &lt; 0.0001), with comparable complete response rates. While incidences of cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome were similar, grade ≥3 cytopenias were more frequent with CAR-T. Notably, GPRC5D-targeted CAR-T yielded higher ORRs than BCMA-targeted constructs (86% vs 66%; <i>p</i> = 0.0006). Furthermore, patients with prior exposure to BCMA bispecific antibodies exhibited lower response rates compared to those with prior CAR-T exposure (71% vs 86%; <i>p</i> = 0.0404). In addition, studies with a median interval of ≥10 months demonstrated significantly higher ORRs than those with &lt;10 months (70% vs 50%; <i>p</i> = 0.0146). In conclusion, GPRC5D CAR-T demonstrates superior efficacy to engineered antibodies in the post-BCMA setting. These findings support prioritising earlier CAR-T use and underscore the importance of antigen selection in optimising treatment sequencing.</p><p></p>

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Subsequent CAR-T and engineered antibody for relapsed/refractory multiple myeloma following BCMA-targeted treatment: a systematic review and meta-analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月14日

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  • Yun Kang,
  • Qiaolin Liu,
  • Lin Liu,
  • Wei Xie,
  • Chunyan Sun,
  • Heng Mei

摘要

Relapse following B-cell maturation antigen (BCMA)-directed therapies represents a critical challenge in relapsed/refractory multiple myeloma (R/R MM). We performed a systematic review and meta-analysis of 34 studies (n = 1280) published between 2020 and 2025 to evaluate salvage CAR-T versus engineered antibody therapies post-BCMA exposure. The pooled overall response rate (ORR) was 60%. CAR-T therapy achieved significantly superior ORR compared to antibody-based approaches (77% vs 52%; p < 0.0001), with comparable complete response rates. While incidences of cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome were similar, grade ≥3 cytopenias were more frequent with CAR-T. Notably, GPRC5D-targeted CAR-T yielded higher ORRs than BCMA-targeted constructs (86% vs 66%; p = 0.0006). Furthermore, patients with prior exposure to BCMA bispecific antibodies exhibited lower response rates compared to those with prior CAR-T exposure (71% vs 86%; p = 0.0404). In addition, studies with a median interval of ≥10 months demonstrated significantly higher ORRs than those with <10 months (70% vs 50%; p = 0.0146). In conclusion, GPRC5D CAR-T demonstrates superior efficacy to engineered antibodies in the post-BCMA setting. These findings support prioritising earlier CAR-T use and underscore the importance of antigen selection in optimising treatment sequencing.