嵌合抗原受体(CAR)T细胞疗法是一种针对肿瘤细胞的工程化T细胞的动态疗法,对于侵袭性复发/难治性血液系统恶性肿瘤,这提供了令人印象深刻的长期缓解。然而,包括严重感染在内的副作用可能危及生命。多重因素,包括细胞因子释放综合征,B细胞再生障碍,和低丙种球蛋白血症,导致感染风险。B细胞再生障碍是预期的目标,CD19+靶向CART细胞的肿瘤外效应,并导致低丙种球蛋白血症。我们回顾了目前在食品和药物管理局批准的5种CART细胞疗法和临床试验中评估的其他CART细胞产品中观察到的低丙种球蛋白血症。并讨论低球蛋白血症的发病,持续时间,免疫恢复。我们回顾了低丙种球蛋白血症和感染之间的关联,由其他已知的B细胞消耗环境提供的讨论。确定了儿童和成人之间低丙种球蛋白血症的差异。我们从临床研究中整合了评估和免疫球蛋白替代的管理策略,专家建议,和组织指南。值得注意的是,我们的评论还重点介绍了针对不同B细胞抗原的新型CART细胞产品,包括B细胞成熟抗原,信号淋巴细胞活化分子,和κ轻链。最后,我们确定了未来研究的关键领域,以减轻和治疗这种转化疗法导致的低丙种球蛋白血症.
Chimeric antigen receptor (CAR) T-cell therapy is a dynamic therapy of engineered T cells targeting neoplastic cells, which offers impressive long-term remissions for aggressive relapsed/refractory hematologic malignancies. However, side effects including severe infections can be life-threatening. Multiple factors, including cytokine release syndrome, B-cell aplasia, and hypogammaglobulinemia, contribute to infection risk. B-cell aplasia is an expected on-target, off-tumor effect of CD19+-targeted CAR T cells and leads to hypogammaglobulinemia. We review hypogammaglobulinemia observed in the 5 currently Food and Drug Administration-approved CAR T-cell therapies and other CAR T-cell products evaluated in clinical trials, and discuss hypogammaglobulinemia onset, duration, and immune recovery. We review associations between hypogammaglobulinemia and infections, with a discussion informed by other known B-cell-depleting contexts. Differences in hypogammaglobulinemia between children and adults are identified. We integrate management strategies for evaluation and immunoglobulin replacement from clinical studies, expert recommendations, and organizational guidelines. Notably, our review also highlights newer CAR T-cell products targeting different B-cell antigens, including B-cell maturation antigen, signaling lymphocytic activation molecule, and κ light chains. Finally, we identify key areas for future study to mitigate and treat hypogammaglobulinemia resulting from this transformative therapy.