Kampouri Eleftheria, Walti Carla S, Gauthier Jordan, Hill Joshua A
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Department of Medicine, Infectious Diseases Service, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Expert Rev Hematol. 2022 Apr;15(4):305-320. doi: 10.1080/17474086.2022.2063833. Epub 2022 Apr 11.
The unprecedented success of chimeric antigen receptor (CAR)-T-cell therapy in the management of B-cell malignancies comes with a price of specific side effects. Healthy B-cell depletion is an anticipated 'on-target' 'off-tumor' side effect and can contribute to severe and prolonged hypogammaglobulinemia. Evidence-based guidelines for the use of immunoglobulin replacement therapy (IGRT) for infection prevention are lacking in this population.
This article reviews the mechanisms and epidemiology of hypogammaglobulinemia and antibody deficiency, association with infections, and strategies to address these issues in CD19- and BCMA-CAR-T-cell recipients.
CD19 and BCMA CAR-T-cell therapy result in unique immune deficits due to depletion of specific B-lineage cells and may require different infection prevention strategies. Hypogammaglobulinemia before and after CAR-T-cell therapy is frequent, but data on the efficacy and cost-effectiveness of IGRT are lacking. Monthly IGRT should be prioritized for patients with severe or recurrent bacterial infections. IGRT may be more broadly necessary to prevent infections in BCMA-CAR-T-cell recipients and children with severe hypogammaglobulinemia irrespective of infection history. Vaccinations are indicated to augment humoral immunity and can be immunogenic despite cytopenias; re-vaccination(s) may be required. Controlled trials are needed to better understand the role of IGRT and vaccines in this population.
嵌合抗原受体（CAR）-T细胞疗法在治疗B细胞恶性肿瘤方面取得了前所未有的成功，但也伴随着特定的副作用。健康B细胞的耗竭是一种预期的“靶向”“非肿瘤”副作用，可导致严重且持续时间长的低丙种球蛋白血症。在这一人群中，缺乏关于使用免疫球蛋白替代疗法（IGRT）预防感染的循证指南。
本文综述了低丙种球蛋白血症和抗体缺乏的机制、流行病学、与感染的关联，以及在接受CD19和BCMA CAR-T细胞治疗的患者中解决这些问题的策略。
由于特定B系细胞的耗竭，CD19和BCMA CAR-T细胞疗法会导致独特的免疫缺陷，可能需要不同的感染预防策略。CAR-T细胞治疗前后低丙种球蛋白血症很常见，但缺乏关于IGRT疗效和成本效益的数据。对于有严重或复发性细菌感染的患者，应优先考虑每月进行IGRT。无论感染史如何，对于接受BCMA CAR-T细胞治疗的患者和患有严重低丙种球蛋白血症的儿童，可能更广泛地需要IGRT来预防感染。建议进行疫苗接种以增强体液免疫，尽管存在血细胞减少，疫苗仍可能具有免疫原性；可能需要再次接种疫苗。需要进行对照试验，以更好地了解IGRT和疫苗在这一人群中的作用。
