7573 Background: Bispecific T-cell–engaging (BiTE) antibodies have transformed the treatment of relapsed or refractory multiple myeloma (MM) but are associated with high rates of infectious complications. Talquetamab, a GPRC5D-directed BiTE, induces immune dysfunction but has been shown to be associated with less infection risk than anti-BCMA BiTEs. Although there is evidence supporting prophylactic intravenous immunoglobulin (IVIG) use for pts receiving anti-BCMA BiTEs, there is limited data assessing the benefit of early IVIG use in patients treated with talquetamab. Methods: A retrospective multicenter cohort study using the TriNetX Research Network to evaluate outcomes among adults with MM treated with talquetamab. Patients who received IVIG within 4 weeks of talquetamab initiation were compared to those who did not receive IVIG within 4 weeks. Propensity score matching was performed which included comorbidities, demographics, prior therapies (PIs, ImIDs, anti-CD38 abs, other BiTEs, belantamab, SCTx and CAR T), lab markers of disease severity, IgG levels, EM disease and plasma cell leukemia. Primary outcomes were 1-year all-cause mortality and infection incidence. Secondary outcomes included infection subtypes and ICU admission. Multivariable Cox proportional hazards models were used to identify independent associations. Results: Among 834 pts treated with talquetamab, 305 received IVIG within 4 wks of initiation. After propensity score matching, 271 patients remained in each cohort with balanced baseline characteristics. Early IVIG use was associated with lower 1-year mortality (14.8% vs. 26.7%; OR, 0.48; 95% CI, 0.31–0.74) and fewer infections of any type (41.7% vs. 55.0%; OR, 0.59; 95% CI, 0.42–0.82). Reductions were most pronounced for respiratory and bloodstream infections. In multivariable analysis, early IVIG remained independently associated with lower hazard of mortality (HR, 0.52; 95% CI, 0.37–0.73). In addition, a sub-analysis comparing early IVIG with no IVIG exposure within 1 year found similar findings. Conclusions: Early IVIG administration following talquetamab initiation was associated with reduced infection risk and improved survival in a large real-world cohort. These findings support consideration of early IVIG as part of routine supportive care for patients receiving talquetamab. Outcome (after propensity matching) IVIG within 4 weeks (n=271) No IVIG within 4 weeks (n=271) OR 95% CI P-value 1-year mortality 40 (14.8) 72 (26.7) 0.48 0.31–0.74 0.0008 Any infection 113 (41.7) 149 (55.0) 0.59 0.42–0.82 0.002 Respiratory infections 37 (13.6) 55 (20.3) 0.62 0.39–0.98 0.04 Bloodstream infections 39 (14.4) 61 (22.5) 0.58 0.37–0.90 0.016 Opportunistic infections 13 (4.8) 10 (3.6) 1.31 0.57–3.05 >0.2 Skin & Soft Tissue infections 12 (4.4) 10 (3.6) 1.21 0.51–2.85 >0.2 Urinary tract infections 12 (4.4) 13 (4.8) 0.92 0.41–2.05 >0.2
O’Brien et al. (Thu,) studied this question.