B-cell-maturation-antigen (BCMA)-directed therapies are highly active for multiple myeloma, but infections are emerging as a major challenge. In this retrospective, single-center analysis we evaluated infectious complications after BCMA-targeted chimeric-antigen-receptor T-cell therapy (CAR-T), bispecific-antibodies (BsAb) and antibody-drug-conjugates (ADC). The primary endpoint was severe (grade ≥3) infection incidence. Amongst 256 patients, 92 received CAR-T, 55 BsAb and 109 ADC. The incidence of severe infections was higher with BsAb (40%) than CAR-T (26%) or ADC (8%), including grade 5 infections (7% vs 0% vs 0%, respectively). Comparing T-cell redirecting therapies, the incidence rate of severe infections was significantly lower with CAR-T compared to BsAb at 1-year (incidence-rate-ratio [IRR] = 0.43, 95%CI 0.25−0.76, P = 0.004). During periods of treatment-emergent hypogammaglobulinemia, BsAb recipients had higher infection rates (IRR:2.27, 1.31−3.98, P = 0.004) and time to severe infection (HR 2.04, 1.05–3.96, P = 0.036) than their CAR-T counterparts. During periods of non-neutropenia, CAR-T recipients had a lower risk (HR 0.44, 95%CI 0.21−0.93, P = 0.032) and incidence rate (IRR:0.32, 95% 0.17–0.59, P < 0.001) of severe infections than BsAb. In conclusion, we observed an overall higher and more persistent risk of severe infections with BsAb. Our results also suggest a higher infection risk during periods of hypogammaglobulinemia with BsAb, and with neutropenia in CAR-T recipients.
针对B细胞成熟抗原（BCMA）的疗法对多发性骨髓瘤具有高度活性，但感染正成为一项主要挑战。在这项回顾性单中心分析中，我们评估了BCMA靶向嵌合抗原受体T细胞疗法（CAR-T）、双特异性抗体（BsAb）和抗体药物偶联物（ADC）后的感染并发症。主要终点为严重（≥3级）感染发生率。在256例患者中，92例接受CAR-T治疗，55例接受BsAb治疗，109例接受ADC治疗。BsAb的严重感染发生率（40%）高于CAR-T（26%）或ADC（8%），包括5级感染（分别为7%对0%对0%）。比较T细胞重定向疗法，CAR-T在1年时的严重感染发生率显著低于BsAb（发生率比[IRR] = 0.43，95%CI 0.25−0.76，P = 0.004）。在治疗相关低丙种球蛋白血症期间，BsAb受者的感染发生率（IRR:2.27，1.31−3.98，P = 0.004）和发生严重感染的时间（HR 2.04，1.05–3.96，P = 0.036）均高于CAR-T受者。在非中性粒细胞减少期间，CAR-T受者的严重感染风险（HR 0.44，95%CI 0.21−0.93，P = 0.032）和发生率（IRR:0.32，95% 0.17–0.59，P < 0.001）均低于BsAb受者。总之，我们观察到BsAb治疗的严重感染总体风险更高且更持久。我们的结果还提示，BsAb在低丙种球蛋白血症期间以及CAR-T受者在中性粒细胞减少期间的感染风险更高。
Comparison of infectious complications with BCMA-directed therapies in multiple myeloma
肿瘤(癌症)患者之家