抗 CD38 单克隆抗体疗法对多发性骨髓瘤患者 CD34+ 造血干细胞动员、采集和移植的影响--系统性综述

Pharmaceuticals Pub Date : 2024-07-15 DOI:10.3390/ph17070944
Flavia Bigi, Enrica Manzato, S. Barbato, Marco Talarico, Michele Puppi, Simone Masci, Ilaria Sacchetti, Roberta Restuccia, Miriam Iezza, I. Rizzello, Chiara Sartor, K. Mancuso, L. Pantani, P. Tacchetti, Michele Cavo, E. Zamagni
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摘要

本系统性综述研究了在临床试验和实际生活中使用抗CD38单克隆抗体达拉单抗和伊沙妥昔单抗治疗多发性骨髓瘤患者的CD34+细胞动员、收集和移植的现有临床数据。2019年至2024年2月期间共发表了26篇临床报告。与对照组相比,大多数研究记录了动员后较低的循环CD34+细胞,导致更高的普乐沙福需求。虽然约半数研究的收集率明显较低,但达拉曲单抗和伊沙妥昔单抗治疗患者与未治疗患者达到收集目标的比例相似,自体干细胞移植(ASCT)的机会也相当。这可能是由于抗CD38单克隆抗体治疗的患者中,普乐沙福的疗效得以保留,而基于化疗或疏导的动员方案均未被证明具有优越性。半数研究报告称,达拉曲单抗和伊沙妥昔单抗治疗患者的ASCT后造血重建较慢,但没有出现过多感染并发症。虽然在体外没有观察到对干细胞的直接影响,但新出现的证据表明,达拉土单抗治疗后,CD34+细胞粘附可能出现失调。总之,抗CD38单克隆抗体似乎会干扰CD34+细胞的动员,但不会持续导致显著的临床后果。需要进一步研究以阐明其潜在机制,并确定该患者群体的最佳动员策略。
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Impact of Anti-CD38 Monoclonal Antibody Therapy on CD34+ Hematopoietic Stem Cell Mobilization, Collection, and Engraftment in Multiple Myeloma Patients—A Systematic Review
This systematic review examines the available clinical data on CD34+ cell mobilization, collection, and engraftment in multiple myeloma patients treated with the anti-CD38 monoclonal antibodies daratumumab and isatuximab in clinical trials and in real life. Twenty-six clinical reports were published between 2019 and February 2024. Most studies documented lower circulating CD34+ cells after mobilization compared to controls, leading to higher plerixafor requirements. Although collection yields were significantly lower in approximately half of the studies, the collection target was achieved in similar proportions of daratumumab- and isatuximab-treated and nontreated patients, and access to autologous stem cell transplant (ASCT) was comparable. This could be explained by the retained efficacy of plerixafor in anti-CD38 monoclonal antibody-treated patients, while no chemotherapy-based or sparing mobilization protocol proved superior. Half of the studies reported slower hematopoietic reconstitution after ASCT in daratumumab- and isatuximab-treated patients, without an excess of infectious complications. While no direct effect on stem cells was observed in vitro, emerging evidence suggests possible dysregulation of CD34+ cell adhesion after daratumumab treatment. Overall, anti-CD38 monoclonal antibodies appear to interfere with CD34+ cell mobilization, without consistently leading to significant clinical consequences. Further research is needed to elucidate the underlying mechanisms and define optimal mobilization strategies in this patient population.
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