CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Influence of PPM1D Mutations on Response and Survival Outcomes Following Bispecific Antibody Therapy in Relapsed and Refractory Multiple Myeloma Patients.
Influence of PPM1D Mutations on Response and Survival Outcomes Following Bispecific Antibody Therapy in Relapsed and Refractory Multiple Myeloma Patients.
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我们开展了一项单中心回顾性研究，纳入27例于2022年6月至2025年9月期间接受bsAb（teclistamab、elranatamab或talquetamab）治疗且治疗前有可用遗传样本的RRMM患者。评估PPM1D突变对治疗反应、无进展生存期（PFS）和总生存期（OS）的影响。
队列中PPM1D突变的检出率为27%。与无PPM1D突变患者相比，突变携带者达到深度缓解的比例呈较低趋势，且6个月PFS（43% vs. 85%，p=0.0272）和6个月OS（57% vs. 90%，p=0.0473）显著较差。
这些发现提示，PPM1D突变可能是接受bsAb治疗的RRMM患者的一种有前景的生物标志物。仍需更大规模的前瞻性研究验证并进一步阐明这些观察结果。
Background/Objectives: Therapeutic options for patients with relapsed and refractory multiple myeloma (RRMM) have advanced substantially in recent years. In particular, T-cell-engaging therapies, including chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies (bsAbs), have emerged as highly effective treatment modalities.
However, data on predictive biomarkers for response to these therapies remain limited. Patients currently receiving T-cell-engaging therapies are typically heavily pretreated and frequently exhibit clonal hematopoiesis. Clonal hematopoiesis, especially involving PPM1D mutations, may adversely affect the efficacy of T-cell-engaging therapies.
Methods: We conducted a retrospective, single-center study including 27 patients with RRMM who were treated with bsAbs (teclistamab, elranatamab, or talquetamab) between June 2022 and September 2025 and for whom genetic material was available before bsAB treatment.
We evaluated the impact of PPM1D mutations on treatment response, progression-free survival (PFS), and overall survival (OS). Results: The prevalence of PPM1D mutations in our cohort was 27%. Compared with patients without PPM1D mutations, mutation carriers showed a trend toward less deep remissions and demonstrated significantly inferior 6-month PFS (43% vs.
85%, p = 0. 0272) and 6-month OS (57% vs. 90%, p = 0. 0473). Conclusions: These findings suggest that PPM1D mutations may represent a promising biomarker in patients with RRMM treated with bsAbs. Larger, prospective studies are warranted to validate and further elucidate these observations.
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