Al-Ola A Abdallah, Associate Professor and Plasma Cell Disorder Program Director of the Division of HMCT at the University of Kansas Medical Center, shared on X:
“Thread: BCMA- and GPRC5D-directed Bispecific Antibodies in RRMM – My Critique and Takeaways.
1. This systematic review/meta-analysis of 15 studies (17 cohorts; 1,900 patients) confirms that BCMA- and GPRC5D-directed bispecific antibodies remain highly active in heavily pretreated RRMM.
2. Key efficacy findings:
- ORR: 65.9%
- ≥VGPR: 51.0%
- ≥CR: 38.2%
- Median PFS: 8.8 months
These results reinforce bispecific antibodies as an effective off-the-shelf immunotherapy option.
3. Safety remains the biggest challenge:
- CRS: 67.5%
- Infections: 60.3% (Grade ≥3: 38.3%)
- Grade ≥3 neutropenia: 42.6%
Supportive care, infection prophylaxis, and monitoring remain essential.
4. Critique 1: Most included studies were single-arm trials or retrospective real-world cohorts. Without randomized comparisons, estimating the true benefit over alternative therapies remains difficult.
Critique 2: There was substantial heterogeneity across studies:
- Different bispecifics (BCMA vs GPRC5D)
- Variable patient populations
- Different prior BCMA exposure
- Mixed trial phases and real-world cohorts
Pooling these together limits direct clinical interpretation.
5. Major limitation: The overall certainty of evidence was low to very low despite moderate methodological quality. High-quality randomized studies are still needed to define the optimal role of bispecific antibodies.
6. Another limitation is that this analysis combines multiple agents with different biology and toxicity profiles. It cannot fully answer the most important clinical questions:
- Which bispecific is best?
- Who should receive BCMA vs GPRC5D first?
- What is the optimal sequencing with CAR-T?
7. Future studies should focus on:
- Head-to-head comparisons
- Biomarker-driven patient selection
- Optimal sequencing after CAR-T or prior bispecific therapy
- Strategies to reduce infections and prolonged cytopenias.
8. Take-home message
Bispecific antibodies have transformed RRMM care by providing rapidly available, highly active immunotherapy. However, maximizing their benefit will depend on better sequencing strategies, proactive toxicity management, and stronger prospective comparative evidence.”
Title: Efficacy and safety of BCMA- or GPRC5D-directed CD3 bispecific antibodies in relapsed/refractory multiple myeloma: a systematic review and meta-analysis of prospective clinical trials and real-world studies
Authors: Jiashun Li, Ainikaer Abulaiti, Deyu Li, Yan Zhao, Paerhati Wahafu, Maerdan Maimaitiming, Shi Qiu, Yuxiang Zhang, Yaqin An, Wenxing Wang, Liangquan Shi, Maihemuti Yakufu, Li Shu, Guohua Li, Zhen Liu
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