Effect of Intravenous Immunoglobulin (IVIG) Supplementation on infection-free survival in recipients of BCMA-directed bispecific antibody therapy for multiple myeloma

Abstract

The main objective of this multi-institutional study is to understand the effect of primary intravenous immunoglobulin (IVIG) replacement on clinical outcomes in recipients of BCMA-directed bispecific antibody (bsAb), where infection remains an important cause of morbidity and mortality. This is a retrospective study of patients treated with either standard of care teclistamab or BCMA-directed investigational bsAb between Nov 2017 and Dec 2023. Primary IVIG prophylaxis was defined as starting IVIG prior to first documented infection. All analyses were adjusted for immortal-time bias inherent in this grouping. A total of 225 patients were included in this analysis. Primary IVIG prophylaxis was defined as starting IVIG prior to first documented infection. The median follow-up of patients treated with and without primary IVIG prophylaxis was, 9 and 11 months, respectively. The cumulative incidence of all grade infections at 12 months with and without primary IVIG prophylaxis were 56% (95%CI 40%,78%) and 60% (95% CI 48%, 76%); p = 0.72, respectively. The 12-month cumulative incidence of ≥ grade 3 infections was 35% (95% CI 21%, 57%) with primary IVIG prophylaxis and 45% (95% CI 34%, 60%) without; p = 0.37. The median infection free survival (IFS) for all-grade infections was 7.7 (95% CI 3.3, 14) months with primary IVIG prophylaxis and 3 (95% CI 2.6, 4.5) months without (p = 0.021). The median ≥ grade 3 IFS was 14 (95% CI 8.8, NR) and 7.5 (95% CI 6.1, 14) months, with and without primary IVIG respectively; p = 0.022. Patients on primary IVIG prophylaxis had a superior progression-free-survival (PFS) [median PFS 15 vs 8 months; p = 0.026] and overall-survival (OS) [median OS 16 vs 44 months; p = 0.007]. On multivariate analysis, primary IVIG prophylaxis was independently associated with improved OS (HR = 0.37; p = 0.021), while the presence of extra-medullary (HR = 2.71; p = <0.001) and high-risk disease (HR = 1.88; p = 0.031) conferred poor outcomes. In recipients of BCMA-directed bsAb, IVIG supplementation was associated with an improved clinical outcome, including favorable IFS and OS.

Fig. 1. Infection-free-survival.

Infection-free-survival for all-grade infection (A) and ≥ grade 3 infection (B) in patients treated with and without primary IVIG.

Fig. 2

Kaplan-Meier curve showing progression-free survival in patients with myeloma treated with BCMA-directed bispecific antibody therapy, stratified by IVIG status.

Fig. 3

Kaplan-Meier curve showing overall survival in patients with myeloma treated with BCMA-directed bispecific antibody therapy, stratified by IVIG status.