CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Practical recommendations for infectious prophylaxis and vaccination in multiple myeloma patients.
Practical recommendations for infectious prophylaxis and vaccination in multiple myeloma patients.
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感染仍是多发性骨髓瘤(MM)发病和死亡的主要原因,这是疾病诱导的免疫功能障碍与治疗相关免疫抑制之间相互作用的结果。蛋白酶体抑制剂、免疫调节药物、单克隆抗体、双特异性抗体和CAR-T(CAR-T)细胞疗法的引入显著改善了生存,同时重塑了感染风险格局。不同治疗策略通过不同机制损害免疫。传统化疗和一些靶向药物主要通过中性粒细胞减少增加细菌感染风险。
然而,现代免疫疗法产生深刻且持久的低丙种球蛋白血症以及细胞免疫缺陷,使患者易发生病毒再激活和机会性感染。靶向BCMA的疗法(特别是双特异性抗体和CAR-T 细胞)导致持续性浆细胞耗竭和持久的体液免疫损害,导致感染模式可在治疗完成后持续很长时间。有效的预防需要风险分层方法,考虑疾病分期、治疗方案、累积免疫抑制和个体患者特征。本综述综合当前证据,并提供实用的、针对具体治疗的建议,涵盖感染风险评估、治疗前筛查、抗菌和抗真菌预防、抗病毒策略、免疫球蛋白替代、粒细胞集落刺激因子使用和疫苗接种。重点放在双特异性抗体和CAR-T 细胞疗法上,这些疗法感染风险最大,预防策略发展最快。免疫球蛋白替代疗法被强调为一种日益重要的支持治疗策略,近期观察性研究将其使用与严重感染的显著减少相关联,并且在接受抗BCMA双特异性抗体的患者中,与生存期改善相关。本综述为临床医生在不断演变的MM治疗格局中提供了个体化感染预防的实用框架。
Infections remain a major cause of morbidity and mortality in multiple myeloma (MM), driven by the interplay between disease-induced immune dysfunction and treatment-related immunosuppression. The introduction of proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, bispecific antibodies, and chimeric antigen receptor T (CAR-T) cell therapy has markedly improved survival while simultaneously reshaping the infectious risk landscape. Different treatment strategies compromise immunity in distinct mechanisms. Conventional chemotherapy and some targeted agents primarily increase the risk of bacterial infections through neutropenia. Modern immunotherapies, however, produce profound and prolonged hypogammaglobulinemia alongside cellular immune deficits, predisposing patients to viral reactivation and opportunistic infections. BCMA-targeting therapies (particularly bispecific antibodies and CAR-T cells) cause sustained plasma cell depletion and durable humoral immune impairment, resulting in an infection pattern that can persist well beyond treatment completion.
Effective prevention requires a risk-stratified approach accounting for disease stage, treatment regimen, cumulative immunosuppression, and individual patient characteristics. This review synthesizes current evidence and provides practical, treatment-specific recommendations spanning infection risk assessment, pre-treatment screening, antimicrobial and antifungal prophylaxis, antiviral strategies, immunoglobulin replacement, granulocyte colony-stimulating factor use, and vaccination.
Emphasis is placed on bispecific antibodies and CAR-T cell therapies, where infectious risk is greatest and prophylactic strategies are evolving most rapidly.
Immunoglobulin replacement is highlighted as an increasingly relevant supportive strategy, with recent observational studies linking its use to marked reductions in serious infections and, among recipients of anti-BCMA bispecific antibodies, improved survival. This review provides clinicians with a practical framework for individualized infection prevention in the evolving therapeutic landscape of MM.
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