Monthly IVIG Lowers Recurrent Infection Rates in Patients With CLL

Monthly intravenous immunoglobulin (IVIG) prophylaxis was associated with a substantial reduction in clinically significant infections among patients with chronic lymphocytic leukemia (CLL) and hypogammaglobulinemia, according to a single-center retrospective cohort study published in Cancer Research Communications.¹

Investigators at the University of California, San Diego reviewed outcomes for 52 patients with CLL who began IVIG between 2005 and 2022, comparing infection rates in the 12 months before treatment initiation with the 12 months afterward.

All 52 patients (100%) had experienced at least 1 infection of grade 2 or higher, per CTCAE, in the year before starting IVIG, with a mean of 2.1 infections per patient during that period. A grade 2 or higher infection was defined as an event requiring oral antimicrobials or outpatient management.

Following initiation of IVIG—dosed at 0.4 g/kg every 28 days in accordance with National Comprehensive Cancer Network guidelines—17 patients (33%) experienced a grade 2 or higher infection in the subsequent 12 months, and the mean per-patient infection count dropped to 0.4. The relative risk reduction (RR) was 67% (RR, 0.33; 95% CI, 0.22-0.48; P <.0001), with a corresponding absolute RR of 67% and a number needed to treat of 1.5.

For patients with CLL, infections are a common and major complication arising from immunosuppression caused by both the disease itself and its treatment.² Based on these findings, the authors characterized IVIG as an effective supportive-care strategy in this patient population. “These findings suggest that IVIG may yield meaningful improvements in patient quality of life by reducing infections,” they wrote in the publication.

Patient Characteristics

The median patient age at IVIG initiation was 68 years, with a mean interval of 9.3 years from CLL diagnosis to IVIG start; the median age at diagnosis was 58 years (IQR, 52-64). Mean baseline immunoglobulin G (IgG) concentration prior to IVIG was 389 mg/dL (range, 93-891 mg/dL). Seventy-five percent of patients had baseline IgG below the 500 mg/dL threshold commonly used to guide initiation of immunoglobulin replacement therapy; the remaining 13 patients were started on IVIG based on clinical concern for immune dysfunction and recurrent infections despite IgG levels above that threshold. Seventy-seven percent of patients had received prior or concurrent CLL-directed therapy.

Neither baseline IgG (P =.79) nor baseline IgA(P =.22), nor recent exposure to CLL-directed therapy (P =.91), was a statistically significant predictor of post IVIG infection risk in this cohort. Among patients who developed an infection after starting IVIG, the median trough IgG level was 703 mg/dL, comparable to the median trough of 687 mg/dL among patients who remained infection-free. The study authors indicated that this finding suggests reaching a target IgG level alone does not fully account for the observed reduction in infections, and that hypogammaglobulinemia represents only one component of the broader immune dysfunction associated with CLL.

Clinical Context

The authors noted that these findings differed slightly from a previous large real-world analysis that did not find a significant reduction in serious infection-related hospitalizations among patients with CLL who received regular immunoglobulin replacement therapy; that analysis reported that serious infections tended to cluster around the time of therapy initiation, reinitiation, and discontinuation.³ The study authors proposed that their use of continuous monthly IVIG dosing, along with detailed chart-level review capturing lower-grade infections, may account for the differing results, and they recommended that future prospective studies of IVIG incorporate patient-reported quality-of-life measures.

The retrospective design, single-center setting, and study period—which largely preceded widespread use of Bruton tyrosine kinase inhibitors and venetoclax (Venclexta)—limit the generalizability of these findings. The authors also noted that outcomes following IVIG discontinuation were not evaluated, and that potential effects of the COVID-19 pandemic on infection patterns during the later study years were not controlled for.

REFERENCES

1. Shah NN, Patel T, Kipps TJ, Choi MY. Intravenous Immunoglobulin Reduces Infections for Patients with Chronic Lymphocytic Leukemia: A Single-Center Retrospective Analysis. Cancer Res Comm. 2026;6(5):1146-1150. doi:10.1158/2767-9764.crc-26-0177

2. Guarana M, Nucci M. Infections in patients with chronic lymphocytic leukemia. Hematol Transfus Cell Ther. 2023;45(3):387-393. doi:10.1016/j.htct.2023.05.006

3. Carrillo de Albornoz S, Zhang X, Arnolda R, et al. Immunoglobulin use, survival, and infection outcomes in patients with chronic lymphocytic leukemia. Blood Adv. 2025;9(20):5367-5377. doi:10.1182/bloodadvances.2025015867