Abstract 6310: Reduction of infections with intravenous immunoglobulin in chronic lymphocytic leukemia: A single-center retrospective analysis

Abstract Hypogammaglobulinemia is common in chronic lymphocytic leukemia (CLL). Guidelines recommend Intravenous Immunoglobulin (IVIG) prophylaxis for patients with recurrent, serious infections (e.g., those requiring IV antibiotics or hospitalization) and IgG < 500 mg/dL. Prior trials showed reduced infections with IVIG without survival benefit, but predate modern CLL therapy. This study evaluates infectious outcomes in CLL patients who received IVIG between 2005 - 2022. This was a single-institution retrospective cohort study of CLL patients. Patients were identified by IVIG receipt and excluded if IVIG was given for other indications (e.g., autoimmune hemolytic anemia). Infection frequency and severity were assessed during the year prior to and the year following IVIG initiation. Treatment history, concurrent therapy, and baseline immunoglobulin levels were also collected. Of 79 patients identified with IVIG treatment, 48 met inclusion criteria of IVIG use for hypogammaglobulinemia and infections, based on charts available for close review. The median age at IVIG initiation was 58 years; mean time from CLL diagnosis to IVIG initiation was 10.5 years. At initiation, 52% had Rai stage 0-II disease and 48% had Rai stage III - IV disease. Baseline mean IgG prior to IVIG was 411 mg/dL (range 93 - 894 mg/dL) and baseline mean IgA was 42 mg/dL (range 4 - 177 mg/dL). Pre-IVIG: 73% of patients experienced at least one grade 2 or 3 infection in the year prior to initiation of IVIG. Most patients had recurrent infections; the average number of grade 2 or higher infections was 1.6 (range 0 - 4). Only two patients had a grade 3 infection in the year prior to IVIG initiation, though notably 15 others had prior grade 3 infections since they were diagnosed with CLL. In total, 17 patients (35%) had a grade 3 infection at any time prior to IVIG. Post-IVIG: Only 12 patients (25%) experienced a grade 2 or higher infection in the year following IVIG initiation, with a mean of 0.375 infections (range 0 - 4). Two of these patients (4%) had grade 3 infections, which were multifocal pneumonia and cellulitis. This represents a 66% relative risk reduction, and a Number Needed to Treat (NNT) of 2.1 to prevent grade 2 or higher infections in the year following IVIG initiation (RR 0.34, P = 0.0001, 95% CI: 0.20 - 0.58). No significant differences were observed between patients with and without post-IVIG infections in prior CLL treatment (75% vs. 83%, p = 0.57), baseline IgG (p = 0.91) or IgA levels (p = 0.93). To conclude, IVIG prophylaxis significantly reduced both moderate (grade 2 or higher) infections, consistent with prior data. While IVIG is recommended primarily for patients with severe infections (2025 NCCN guidelines), our findings suggest IVIG may also meaningfully reduce grade 2 infections and improve quality of life. Future IVIG studies should incorporate quality of life metrics to define the role of IVIG in modern CLL care. Citation Format: Nirja Shah, Tulsi Patel, Thomas J. Kipps, Michael Y. Choi. Reduction of infections with intravenous immunoglobulin in chronic lymphocytic leukemia: A single-center retrospective analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6310.