Harvard Medical School, Boston, MA.
Dana-Farber Cancer Institute, Boston, MA.
Blood Adv. 2023 Sep 26;7(18):5485-5495. doi: 10.1182/bloodadvances.2023010524.
Infections are an important complication after B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy and risks may differ between the early and late periods. We evaluated infections in 99 adults who received a first BCMA-directed CAR T-cell therapy (commercial and investigational autologous BCMA CAR T-cell products at the recommended phase 2 dose) for relapsed/refractory multiple myeloma between November 2016 and May 2022. Infections were recorded until day 365, if patients experienced symptoms with a microbiologic diagnosis, or for symptomatic site-specific infections treated with antimicrobials. One-year cumulative incidence functions were calculated based on time to first respiratory infection using dates of infection-free death and receipt of additional antineoplastic therapies as competing risks. Secondary analysis evaluated risk factors for late respiratory infections using univariate and multivariable Cox regression models. Thirty-seven patients (37%) experienced 64 infectious events over the first year after BCMA-directed CAR T-cell therapy, with 42 early infectious events (days, 0-100), and 22 late infectious events (days, 101-365). Respiratory infections were the most common site-specific infection and the relative proportion of respiratory infections increased in the late period (31% of early events vs 77% of late events). On multivariable analysis, hypogammaglobulinemia (hazard ratio [HR], 6.06; P = .044) and diagnosis of an early respiratory viral infection (HR, 2.95; P = .048) were independent risk factors for late respiratory infection. Respiratory infections predominate after BCMA CAR T-cell therapy, particularly after day 100. Hypogammaglobulinemia and diagnosis of an early respiratory infection are risk factors for late respiratory infections that may be used to guide targeted preventive strategies.
在 B 细胞成熟抗原 (BCMA) 定向嵌合抗原受体 (CAR) T 细胞治疗后，感染是一个重要的并发症，并且在早期和晚期的风险可能不同。我们评估了 99 名接受复发/难治性多发性骨髓瘤的首次 BCMA 定向 CAR T 细胞治疗（推荐的 2 期剂量的商业和研究性自体 BCMA CAR T 细胞产品）的成年人的感染情况。这些患者的感染情况记录到 365 天，如果患者出现症状且有微生物学诊断，或者有症状的特定部位感染接受了抗菌药物治疗。使用无感染死亡和接受额外抗肿瘤治疗的日期作为竞争风险，基于首次呼吸道感染的时间计算了 1 年累积发生率函数。使用单变量和多变量 Cox 回归模型对晚期呼吸道感染的危险因素进行了二次分析。37 名患者（37%）在接受 BCMA 定向 CAR T 细胞治疗后的第一年中经历了 64 次感染事件，其中 42 次为早期感染事件（天，0-100），22 次为晚期感染事件（天，101-365）。呼吸道感染是最常见的特定部位感染，并且在晚期呼吸道感染的比例增加（早期事件中为 31%，晚期事件中为 77%）。在多变量分析中，低丙种球蛋白血症（风险比[HR]，6.06；P=.044）和早期呼吸道病毒感染的诊断（HR，2.95；P=.048）是晚期呼吸道感染的独立危险因素。BCMA CAR T 细胞治疗后，呼吸道感染占主导地位，尤其是在 100 天后。低丙种球蛋白血症和早期呼吸道感染的诊断是晚期呼吸道感染的危险因素，可能用于指导有针对性的预防策略。
