Incidence of severe infections in patients with multiple myeloma treated with immunoglobulin-replacement therapy

Abstract Introduction: Secondary immunodeficiency (SID) is an increasing concern in patients with multiple myeloma (MM). SID may be caused by the disease itself or its treatments and is associated with a higher risk of severe infections and mortality (Giralt et. al., Clin Lymphoma Myeloma Leuk, 2023). These concerns are growing as new agents to treat MM become available, resulting in a greater risk of severe infections and mortality (Mohan et al, Blood Cancer J. 2025). Immunoglobulin replacement therapy (IgRT) is considered in some patients with MM and SID in order to reduce the risk of severe infections (Otani et. al. J Allergy Clin Immunol 2022). The present study aims to assess the effectiveness of 10% Human Intravenous Immunoglobulin Caprylate/Chromatography Purified (IGIV-C10%) on the risk of severe infections in patients with MM and SID. Methods: A retrospective real-world evidence study was conducted using PharMetrics Plus, a health plan claims database of insured US patients. The study included patients diagnosed with MM (defined by ≥2 claims with an ICD-10-CM code for MM spaced ≥30 days apart), who subsequently developed SID (based on the presence of an inpatient or outpatient claim with one of the following ICD-10-CM codes: D80.1, D80.3, D80.9), and who initiated treatment with IGIV-C10% between Jul 1st, 2018, and Jun 30th, 2024. Index date was defined as the first IGIV-C10% dose. Patients were required to have 6-month continuous enrollment before and after index. IGIV-C10% exposure was defined as ≥4 doses of IGIV-C10% during the 6 months after index. Patients treated with IgRT within 12 months prior to index or presenting with an ICD-10-CM code for primary immunodeficiency, or any other conditions for which IgRT is indicated (other than SID) at any point during the study period were excluded. Demographic, clinical, and treatment data were descriptively summarized for the overall study sample. The primary outcome was the occurrence of severe infections, defined as either a hospitalization with an ICD-10-CM code for infection as primary admission code, infections requiring injectable anti-infectives, or infections considered as serious per the FDA Sentinel Initiative (FDA, 2024). The proportion of patients with severe infection during the exposed period (6-month post-IGIV-C10%) was compared to that during the unexposed period (6-month pre-IGIVC-10%). Odds ratios (ORs), 95% confidence intervals (95%CIs), and p-values were estimated. Due to the self-controlled nature of the study design, only time-varying confounders were controlled for in the assessment of the adjusted point estimates; generalized estimating-equation (GEE) logistic regression models adjusted for anti-cancer treatments and quarter and year of index were applied. Results: The study sample consisted of 154 patients with MM, with a mean (SD) age of 64.2 (10.1) years, and 58.4% (N=90) being male. A total of 90 (58.4%) patients had undergone a hematopoietic stem cell transplantation (HSCT) any time in patient history prior to index. During the study period, the most common MM therapeutic agents used were corticosteroids (N=146, 94.8%), B-cell monoclonal antibodies (N=135, 87.7%), immunomodulatory imide drugs (N=122, 79.2%), proteasome inhibitors (N=116, 75.3%), alkylating agents (N=49, 31.8%), bispecific antibodies (N=21, 13.6%), chimeric antigen receptor T-cell therapies (N=15, 9.7%), and antimetabolites (N=13, 8.4%). Distribution of therapies remained relatively stable across the exposed (post-IGIV-C10%) and unexposed (pre-IGIV-C10%) periods. On average, patients received 5.6 (SD = 1.2) doses of IGIV-C10%, with a mean (SD) dose of 19.6 (11.8) grams per encounter. Mean (SD) time between doses was 4.6 (1.0) weeks. After adjusting for anti-cancer therapy use over the exposed and unexposed periods and quarter and year of index, the odds of severe infection were 59% lower during the post-IGIV-C10% period (OR: 0.41; 95%CI: 0.22, 0.78; p<0.01). A significant reduction (68%) in the proportion of patients with any infection was also observed (OR: 0.32 95%CI: 0.18, 0.57; p<0.001).Conclusions: Regular administration of IGIV-C10% (i.e., ≥4 infusions over 6 months) was associated with a significant reduction in the odds of both severe infections and infections of any kind in patients with MM presenting with SID.