Abstract：
OBJECTIVE: Bispecific antibodies (BsAbs) are an effective treatment used in relapsed or refractory multiple myeloma. Despite a well-tolerated safety profile, infectious events appear to be frequent in clinical trials. Real-world data on epidemiology, characteristics, risk factors, and outcomes of infections in patients treated with BsAb are still needed.
METHODS: A retrospective, multicentre study in BsAb-treated patients with multiple myeloma was performed in 14 French centres from December 2020 to February 2023. The primary objective was to describe the incidence of infections that required hospitalization, specific treatment, or adaptation in BsAb administration.
RESULTS: Among 229 patients with multiple myeloma treated with BsAb, 153 (67%) received teclistamab, 47 (20%) received elranatamab, and 29 (13%) talquetamab. We reported a total of 234 infections, including 123 (53%) of grade of ≥3. Predominant infections affected the respiratory tract (n = 116, 50%) followed by bacteraemias (n = 36, 15%). The hospitalization rate was 56% (n = 131), and 20 (9%) infections resulted in death. Global cumulative incidence of the first infection was 70% in all patients, 73% in patients treated with B-cell maturation antigen-targeting, and 51% with GPRC5D-targeting BsAb. In univariate analyses, corticosteroids for cytokine release syndrome (CRS)/immune effector cell-associated neurotoxicity syndrome (ICANS) were associated with a higher risk of first infection (HR = 2.13; 95% CI, 1.38-3.28), whereas GPRC5D-targeting BsAb and anti-bacterial prophylaxis were associated with a lower risk (HR = 0.53; 95% CI, 0.3-0.94 and HR = 0.65; 95% CI, 0.46-0.9). Fine and Gray multivariate model found that only corticosteroids for CRS/ICANS were correlated with a higher risk of first infection (HR = 2.01; 95% CI, 1.27-3.19).
CONCLUSIONS: The implementation of preventive measures that aim to mitigate the risk of infection under BsAb is pivotal, notably in patients who received corticosteroids for CRS/ICANS.
METHODS: A retrospective, multicentre study in BsAb-treated patients with multiple myeloma was performed in 14 French centres from December 2020 to February 2023. The primary objective was to describe the incidence of infections that required hospitalization, specific treatment, or adaptation in BsAb administration.
RESULTS: Among 229 patients with multiple myeloma treated with BsAb, 153 (67%) received teclistamab, 47 (20%) received elranatamab, and 29 (13%) talquetamab. We reported a total of 234 infections, including 123 (53%) of grade of ≥3. Predominant infections affected the respiratory tract (n = 116, 50%) followed by bacteraemias (n = 36, 15%). The hospitalization rate was 56% (n = 131), and 20 (9%) infections resulted in death. Global cumulative incidence of the first infection was 70% in all patients, 73% in patients treated with B-cell maturation antigen-targeting, and 51% with GPRC5D-targeting BsAb. In univariate analyses, corticosteroids for cytokine release syndrome (CRS)/immune effector cell-associated neurotoxicity syndrome (ICANS) were associated with a higher risk of first infection (HR = 2.13; 95% CI, 1.38-3.28), whereas GPRC5D-targeting BsAb and anti-bacterial prophylaxis were associated with a lower risk (HR = 0.53; 95% CI, 0.3-0.94 and HR = 0.65; 95% CI, 0.46-0.9). Fine and Gray multivariate model found that only corticosteroids for CRS/ICANS were correlated with a higher risk of first infection (HR = 2.01; 95% CI, 1.27-3.19).
CONCLUSIONS: The implementation of preventive measures that aim to mitigate the risk of infection under BsAb is pivotal, notably in patients who received corticosteroids for CRS/ICANS.
摘要：
目的：双特异性抗体（BsAb）是用于复发性/难治性多发性骨髓瘤的有效治疗方法。尽管耐受性良好的安全性，感染性事件在临床试验中似乎很常见.关于流行病学的真实世界数据，特点,在接受BsAb治疗的患者中,感染的危险因素和结局仍需要考虑.
方法：回顾性研究，2020年12月至2023年2月，在14个法国中心对BsAb治疗的MM患者进行了多中心研究。主要目的是描述需要住院治疗的感染发生率，具体治疗,或BsAb施用中的适应。
结果：在229例接受BsAb治疗的MM患者中，153（67%）接受了testlistamab，47（20％）接受了elranatamab和29（13％）talquetamab。我们共报告了234例感染,包括123名(53%)≥3级。主要感染影响呼吸道（n=116，50％），其次是菌血症（n=36，15％）。住院率为56%(n=131)，20例（9%）感染导致死亡。在所有患者中，首次感染的全球累积发生率为70％，73％的患者用BCMA靶向治疗，51％的患者用GPRC5D靶向BsAb治疗。在单变量分析中，用于CRS/ICANS的皮质类固醇与较高的首次感染风险相关（HR=2.13;95CI：1.38-3.28），而GPRC5D靶向BsAb和抗菌药物预防与较低的风险相关(HR=0.53;95CI:0.3-0.94和HR=0.65;95CI:0.46-0.9).精细和灰色多变量模型发现，只有用于CRS/ICANS的皮质类固醇与较高的首次感染风险相关（HR=2.01；95CI：1.27-3.19）。
结论：实施旨在降低BsAb感染风险的预防措施至关重要，特别是在接受CRS/ICANS糖皮质激素治疗的患者中。
方法：回顾性研究，2020年12月至2023年2月，在14个法国中心对BsAb治疗的MM患者进行了多中心研究。主要目的是描述需要住院治疗的感染发生率，具体治疗,或BsAb施用中的适应。
结果：在229例接受BsAb治疗的MM患者中，153（67%）接受了testlistamab，47（20％）接受了elranatamab和29（13％）talquetamab。我们共报告了234例感染,包括123名(53%)≥3级。主要感染影响呼吸道（n=116，50％），其次是菌血症（n=36，15％）。住院率为56%(n=131)，20例（9%）感染导致死亡。在所有患者中，首次感染的全球累积发生率为70％，73％的患者用BCMA靶向治疗，51％的患者用GPRC5D靶向BsAb治疗。在单变量分析中，用于CRS/ICANS的皮质类固醇与较高的首次感染风险相关（HR=2.13;95CI：1.38-3.28），而GPRC5D靶向BsAb和抗菌药物预防与较低的风险相关(HR=0.53;95CI:0.3-0.94和HR=0.65;95CI:0.46-0.9).精细和灰色多变量模型发现，只有用于CRS/ICANS的皮质类固醇与较高的首次感染风险相关（HR=2.01；95CI：1.27-3.19）。
结论：实施旨在降低BsAb感染风险的预防措施至关重要，特别是在接受CRS/ICANS糖皮质激素治疗的患者中。
