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

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.