Clinical significance of complete remission and measurable residual disease in relapsed/refractory multiple myeloma patients treated with T-cell redirecting immunotherapy

IF 10.1 1区 医学 Q1 HEMATOLOGY American Journal of Hematology Pub Date : 2024-11-16 DOI:10.1002/ajh.27526
Aintzane Zabaleta, Noemi Puig, Maria-Teresa Cedena, Aina Oliver-Caldes, José J. Perez, Cristina Moreno, Luis-Esteban Tamariz-Amador, Paula Rodriguez-Otero, Felipe Prosper, Veronica Gonzalez-Calle, Lucía López-Corral, Beatriz Rey-Búa, Borja Puertas, Fátima Mirás, José María Sánchez-Pina, Nieves López-Muñoz, Manel Juan, E. Azucena González-Navarro, Álvaro Urbano, Carlos Fernández de Larrea, Joan Blade, Juan-José Lahuerta, Joaquín Martinez-Lopez, Maria-Victoria Mateos, Jesús F. San Miguel, Bruno Paiva
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Abstract

The impact of measurable residual disease (MRD) in relapse/refractory multiple myeloma (RRMM) patients treated with T-cell redirecting immunotherapy is uncertain. We analyzed MRD dynamics using next-generation flow in 201 patients treated in clinical trials with chimeric antigen receptor (CAR) T cells and T-cell engagers (TCE). Achieving MRD negativity at 10−6 was associated with 89% reduction in the risk of progression and/or death. Survival outcomes were improved in patients with sustained versus transient MRD negativity and were dismal in those who remained MRD positive. The intent-to-treat MRD negative rates were higher in patients treated with CAR T cells versus TCE. However, among patients achieving MRD negativity, there were no differences in survival outcomes when stratified according to treatment with CAR T cells versus TCE. In multivariate analysis including the number of prior lines of treatment, International Staging System, cytogenetic risk, extramedullary disease and type of T-cell redirecting immunotherapy, only the complete remission (CR) and MRD statuses showed independent prognostic value for progression-free and overall survival. In conclusion, our study shows that deep and sustained MRD negative CR is the most relevant prognostic factor and should be considered as the treatment endpoint in RRMM patients treated with CAR T cells and TCE.

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接受T细胞重定向免疫疗法治疗的复发/难治性多发性骨髓瘤患者完全缓解和可测量残留疾病的临床意义
在接受T细胞重定向免疫疗法治疗的复发/难治性多发性骨髓瘤(RRMM)患者中,可测量残留疾病(MRD)的影响尚不确定。我们利用新一代流式细胞术分析了在嵌合抗原受体(CAR)T细胞和T细胞吞噬体(TCE)临床试验中接受治疗的201名患者的MRD动态。MRD阴性率达到10-6与病情进展和/或死亡风险降低89%相关。MRD持续阴性与短暂阴性相比,患者的生存状况有所改善,而MRD持续阳性的患者生存状况则不容乐观。接受 CAR T 细胞治疗的患者的意向治疗 MRD 阴性率高于接受 TCE 治疗的患者。然而,在获得 MRD 阴性的患者中,根据 CAR T 细胞治疗与 TCE 治疗进行分层后,生存结果并无差异。在包括既往治疗次数、国际分期系统、细胞遗传学风险、髓外疾病和T细胞重定向免疫疗法类型在内的多变量分析中,只有完全缓解(CR)和MRD状态对无进展生存期和总生存期具有独立的预后价值。总之,我们的研究表明,深度和持续的MRD阴性CR是最相关的预后因素,应被视为接受CAR T细胞和TCE治疗的RRMM患者的治疗终点。
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来源期刊
CiteScore
15.70
自引率
3.90%
发文量
363
审稿时长
3-6 weeks
期刊介绍: The American Journal of Hematology offers extensive coverage of experimental and clinical aspects of blood diseases in humans and animal models. The journal publishes original contributions in both non-malignant and malignant hematological diseases, encompassing clinical and basic studies in areas such as hemostasis, thrombosis, immunology, blood banking, and stem cell biology. Clinical translational reports highlighting innovative therapeutic approaches for the diagnosis and treatment of hematological diseases are actively encouraged.The American Journal of Hematology features regular original laboratory and clinical research articles, brief research reports, critical reviews, images in hematology, as well as letters and correspondence.
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