BISPECIFIC ANTIBODIES AND CART IN MULTIPLE MYELOMA: APPROPRIATE SELECTION OF PATIENTS AND SEQUENCING

医学 推车 多发性骨髓瘤 抗体 选择(遗传算法) 双特异性抗体 计算生物学 内科学 肿瘤科 免疫学 单克隆抗体 人工智能 机械工程 计算机科学 工程类 生物
作者
Michele Puppi,Ilaria Sacchetti,Katia Mancuso,Paola Tacchetti,Lucia Pantani,Ilaria Rizzello,Miriam Iezza,Marisa Talarico,Enrica Manzato,Simone Masci,Roberta Restuccia,Simona Barbato,Silvia Armuzzi,Barbara Taurisano,Ilaria Vigliotta,Elena Zamagni
出处
期刊:Mediterranean Journal of Hematology and Infectious Diseases [Institute of Hematology, Catholic University]
卷期号:17 (1): e2025045-e2025045
标识
DOI:10.4084/mjhid.2025.045
摘要

T-cell redirecting therapies (TCR) marked a step forward in the treatment of relapsed/refractory multiple myeloma (RRMM). These agents, represented by chimeric antigen receptor (CAR) T-cells and bispecific antibodies (BsAbs), proved to ameliorate the prognosis of difficult-to-treat patients in pivotal clinical trials, leading to their introduction into clinical practice. Both strategies rely on recruiting patients' T-cells against specific tumor antigens, with B-cell maturation antigen (BCMA) and G-protein coupled receptor group C family 5 member D (GPRC5D) being the targets most extensively studied. Nevertheless, most of these regimens under the current label do not hesitate in a clear plateau of survival curves, thus raising the scenario of patients receiving more than one TCR agent in sequence. Also, they differ in their toxicity profiles and administration features. Consequently, the appropriate application of these agents mandates a careful selection of the right treatment for the right patient, with the ultimate intent of optimizing patient outcomes. In this respect, practical considerations regarding tumor- and patient-specific features are of high importance. Tailored clinical trials and analysis of real-word experiences are also crucial to produce evidence-based recommendations. Likewise, pre-clinical research is critical for the conceptualization of treatment algorithms potentially driven by immunological clues and knowledge of mechanisms of resistance. In this review we aim at providing practical guidance for defining the most appropriate treatment sequencing and determining the selection of patients for each treatment.
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