Effect of intravenous immunoglobulin on infections in multiple myeloma patients receiving daratumumab

Abstract

Daratumumab is an anti-CD38 monoclonal antibody that has shown clinical benefit in both relapsed/refractory as well as newly diagnosed multiple myeloma (MM). Although daratumumab is very well-tolerated, randomized clinical trial data have consistently demonstrated an increased risk of infection, particularly along the respiratory tract, in patients receiving daratumumab. CD38 is present on healthy plasma cells, and their destruction can lead to hypogammaglobulinemia (HGG). In this study, we retrospectively reviewed all patients with MM treated with daratumumab and intravenous immunoglobulin (IVIG) at our institution from 2015-2019. The primary endpoints were the incidence rate ratios (IRR) of all-grade infections and grade 3-4 infections per patient-year during IVIG versus observation. In addition, a separate reference group of MM patients who were treated with daratumumab but never received IVIG was identified to establish baseline infection rates and to identify differences in baseline characteristics among patients who were selected to receive IVIG. A total of 43 patients received daratumumab and IVIG, primarily in the relapsed/refractory setting. All patients had HGG during treatment with daratumumab, with most (81%) experiencing moderate HGG (IgG <400mg/dL). During periods of IVIG use, all-grade infections were 43% lower and grade 3-4 infections were 70% lower compared to observation periods (no IVIG use). The reference group that had never received IVIG (n=100) had fewer infections in the year prior to daratumumab and a lower infection rate while on daratumumab. In conclusion, selected patients with multiple recurrent infections prior to starting daratumumab derived substantial benefit from the use of IVIG.