PO.CL09.02 · 临床研究

T细胞衔接器在多发性骨髓瘤中的感染风险特征

Characterizing the risk of infections with T-cell engagers in multiple myeloma

编号 6651 展板 20 时间 4/21 02:00–05:00 区域 Section 47 主讲 Lindsay Fogel, BS

分会场 Real World Data to Provide Real World Evidence

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作者与单位 Authors & Affiliations

Lindsay Fogel¹, Harsh Parmar², Shucen Wan³, Adolfo Aleman², Pooja Phull², David Vesole², David S. Siegel², Rena Feinman⁴, Claire L. Carter¹, Noa Biran²

¹Hackensack Meridian School of Medicine, Nutley, NJ,²John Theurer Cancer Center, Hackensack Meridian Health, Hackensack, NJ,³Penn State Health Hershey Medical Center, Hershey, PA,⁴Center for Discovery and Innovation (Hackensack Meridian Health), Nutley, NJ

摘要 Abstract

中文摘要

背景：T细胞衔接器（TCE）在经过大量既往治疗的多发性骨髓瘤患者中已显示出显著疗效；然而，它们与较高的感染风险相关，可能导致发病率和死亡率升高。在此，我们报告在接受TCE治疗的复发/难治性MM患者中感染并发症的经验，描述其发生率、严重程度和危险因素。方法：这是一项单中心回顾性研究，纳入2023年1月至2025年9月间连续接受teclistamab（Tec）、elranatamab（Elra）或talquetemab（Talq）治疗的79例MM患者。从电子病历中收集人口学、基线疾病特征、既往治疗和毒性数据。感染按CTCAE 5.0版分级。采用Kaplan-Meier曲线估算总生存期（OS）和无进展生存期（PFS）。患者被分为发生任何级别感染者与未发生感染者。进行单变量Cox比例风险回归以识别与OS或PFS相关的变量，将有统计学意义的预测因素（p<0.05）纳入多变量分析。结果：79例患者至少接受了一剂tec（n=29，37%）、talq（n=40，51%）或elra（n=10，13%）。中位年龄68岁（范围39-86），56%为女性，患者接受既往治疗的中位线数为5（范围2-18）。44例患者（56%）曾接受过BCMA靶向治疗。36例患者（46%）存在高危细胞遗传学。共报告109起感染事件，患者经历感染事件的中位数为1（范围0-12）。58例患者（73%）发生1-2级CRS。48例患者（61%）发生感染，各TCE的发生率不同：tec 19/29（66%），talq 19/40（48%），elra 8/10（80%）。28例患者（35%）发生3-4级感染。10例患者（13%）需要重症监护，主要因细菌性肺炎或脓毒症。4例患者（5%）因感染并发症停用TCE。11例患者（14%）在接受TCE治疗期间或停药后不久发生感染相关死亡。中位随访11.9个月（95% CI 10.1-14.0）时，整个队列的mPFS为5.5个月（95% CI 3.7-11.3），mOS为16.3个月（95% CI 7.9-21.6）。发生感染的患者结局较未感染者差：PFS 4.2 vs 7.1个月（p=0.3）；OS 6.4 vs 17.4个月（p=0.027）。使用IVIG与PFS改善（14.6 vs 5.7个月，p=0.0002）和OS改善（21.6 vs 7.9个月，p=0.0003）相关。在多变量分析中，感染（HR 2.14，p=0.030）和IVIG（HR 0.28，p=0.009）是OS的独立预测因素，而只有IVIG显著影响PFS（HR 0.27，p=0.0002）。结论：在这项针对接受TCE治疗、经过大量既往治疗的MM患者的单中心分析中，感染并发症很常见，发生率达61%。感染与较差的OS独立相关，而使用IVIG与死亡风险降低72%相关。需要开展前瞻性研究以确定IVIG的最佳时机和用法，从而证明其在接受TCE治疗患者中的疗效。

查看英文原文 English abstract

Background: T-cell engagers (TCE) have demonstrated remarkable efficacy in pts with heavily pretreated multiple myeloma; however, they are associated with a higher risk of infections which can contribute to increased morbidity and mortality. Here, we report our experience with infectious complications in relapsed/refractory MM pts receiving TCEs, characterizing their incidence, severity and risk factors. Methods: This is a single-center retrospective study of 79 consecutive MM pts who received teclistamab (Tec), elranatamab (Elra) or talquetemab (Talq) between 1/2023-9/2025. Demographics, baseline disease characteristics, prior therapies, and toxicities were collected from electronic records. Infections were graded according to CTCAE version 5.0. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier curves. Pts were separated into those with any grade infection versus those without. Univariate Cox proportional hazards regression was performed to identify variables associated with OS or PFS, with significant predictors (p<0.05) included in multivariable analysis. Results: Seventy-nine pts received at least one dose of tec (n=29, 37%), talq (n=40, 51%), or elra (n=10, 13%). Median age was 68 yrs (range 39-86), 56% were female, and pts had a median of 5 prior lines of therapy (range 2-18). 44 pts (56%) had received prior BCMA-directed therapy. High risk cytogenetics were present in 36 pts (46%). A total of 109 infectious events were reported, with pts experiencing a median of 1 infectious event (range 0-12). Grade 1-2 CRS occurred in 58 pts (73%). 48 pts (61%) developed infections with rates varying by TCE: tec 19/29 (66%), talq 19/40 (48%), elra 8/10 (80%). Grade 3-4 infections occurred in 28 pts (35%). 10pts (13%) required intensive care, primarily due to bacterial pneumonia or sepsis. Four pts (5%) discontinued TCE due to infectious complications. 11 pts (14%) experienced infection related mortality while receiving or shortly after discontinuing TCE. At median follow-up of 11.9 mos (95% CI 10.1-14.0), mPFS was 5.5 mos (95% CI 3.7-11.3) and mOS was 16.3 mos (95% CI 7.9-21.6) for the entire cohort. Pts with infections had inferior outcomes compared to those without: PFS 4.2 vs 7.1 mos (p=0.3); OS 6.4 vs 17.4 mos (p=0.027). IVIG use was associated with improved PFS (14.6 vs 5.7 mos, p=0.0002) and OS (21.6 vs 7.9 mos, p=0.0003). On MVA, infection (HR 2.14, p=0.030) and IVIG (HR 0.28, p=0.009) were independent predictors of OS, while only IVIG significantly impacted PFS (HR 0.27, p=0.0002). Conclusion: In this single-center analysis of heavily pretreated MM pts receiving TCEs, infectious complications were frequent, occurring in 61% pts. Infections were independently associated with inferior OS, while use of IVIG was associated with a 72% reduction in risk of death. Prospective studies are required to establish optimal timing and use of IVIG to demonstrate its efficacy in pts receiving TCEs.

利益披露 Disclosure

L. Fogel, None. H. Parmar, Cellectar Other, Personal consulting/advisory role. S. Wan, None.. A. Aleman, None. P. Phull, Pfizer Other, Immediate family member's employment. D. Vesole, Abbvie Stock. Amgen Stock, Other, Speakers' Bureau. Biogen Stock. Bristol-Myers Squibb Stock, Speakers' Bureau. Gilead Sciences Stock. Johnson & Johnson Stock. Lilly Stock. Merck Stock. Novartis Stock. GlaxoSmithKline Other, Speakers' Bureau. Janssen Oncology Other, Speakers' Bureau. Karyopharm Therapeutics Other, Speakers' Bureau. Sanofi Other, Speakers' Bureau. Takeda Other, Speakers' Bureau. D. S. Siegel, COTA Stock. Bristol Myers Squibb Other, Honoraria. Envision Pharma Group Other, Honoraria. Menarini Silicon Biosystems Other, Honoraria. Merck Other, Honoraria. Pfizer Other, Honoraria. Sebia Other, Honoraria. R. Feinman, COTA Stock. Bristol Myers Squibb Other, Immediate family member: Honoraria; Consulting or Advisory Role. Envision Pharma Group Other, Immediate family member: Honoraria; Consulting or Advisory Role. Menarini Silicon Biosystems Other, Immediate family member: Honoraria; Consulting or Advisory Role. Merck Other, Immediate family member: Honoraria; Consulting or Advisory Role. Pfizer Other, Immediate family member: Honoraria; Consulting or Advisory Role. Sebia Other, Immediate family member: Honoraria; Consulting or Advisory Role. C. L. Carter, None. N. Biran, Boehringer Ingelheim Other, Immediate family member's employment. Abbvie Honoraria; Consulting or Advisory Role. Bristol Myers Squibb Other, Honoraria; Consulting or Advisory Role; Speakers' Bureau; Research Funding. Janssen Other, Honoraria; Consulting or Advisory Role; Speakers' Bureau; Research Funding. Pfizer Other, Honoraria; Consulting or Advisory Role. Sanofi Other, Honoraria; Consulting or Advisory Role; Speakers' Bureau. Takeda Other, Honoraria; Consulting or Advisory Role. Amgen Other, Consulting or Advisory Role; Research Funding. GlaxoSmithKline Other, Consulting or Advisory Role. Karyopharm Therapeutics Other, Consulting or Advisory Role; Research Funding. Merck Other, Research Funding.

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