Effect of intravenous immunoglobulin G on mortality among immune checkpoint inhibitor recipients

Summary: Abstract Body: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, considerably improving patient survival across a wide range of cancers. Immune-related adverse events (irAEs) are common toxicities of ICIs and often require management with systemic immunosuppression, which may negatively impact the therapeutic efficacy of ICIs. Of these, intravenous immunoglobulin (IVIG) is an effective treatment for the most severe irAEs, but little is known about its impact on ICI outcomes. Using the TriNetX Research Network drawing from 105 healthcare organizations across the US and Europe, we conducted a retrospective cohort study to investigate the effect of IVIG exposure on overall survival among ICI recipients. We identified 483 patients who received IVIG post-ICI initiation, who were then 1:1 propensity score matched on baseline demographics (age, sex, ethnicity, race), cancer type, and cancer stage to 483 ICI recipients without IVIG exposure (controls). Patients with hematologic malignancies, autoimmune conditions, or IVIG exposure prior to ICI initiation were excluded. To account for immortal time bias, we used landmark analyses at 3, 6, and 12 months following ICI initiation. Using Cox proportional hazard models with 95% confidence intervals, we found IVIG-exposed patients had a significantly increased risk of mortality at 3- (HR [95% CI] = 1.67 [1.24, 2.25], p=0.001), 6- (1.75 [1.18, 2.57], p=0.004), and 12-month (1.77 [1.08, 2.89], p=0.021) landmarks. Sensitivity analyses using both IVIG and intramuscular immunoglobulin (IG) and stratifying by number of IG treatment cycles showed consistent results. Our findings suggest that administering IVIG to ICI recipients significantly increases their risk of mortality, potentially due to accelerated ICI clearance and negative attenuation of immunotherapy, highlighting the need for careful consideration of alternative management strategies for irAEs in patients on ICIs. Debby Cheng¹, Nga Nguyen¹, Christopher J. Thang¹, Olivia Burke¹, Yevgeniy Semenov¹ 1. Massachusetts General Hospital, Boston, MA, United States. Clinical Research: Epidemiology and Observational Research