Introduction:

Hypogammaglobulinemia is common in patients with chronic lymphocytic leukemia (CLL). Per consensus guidelines, Intravenous Immunoglobulin (IVIG) prophylaxis is generally reserved for patients who have had recurrent, serious infections (e.g., those requiring IV antibiotics or hospitalization) and who also have serum IgG < 500 mg/dL.

While prior studies demonstrated reduced infections with IVIG without survival benefit, these were conducted prior to the era of contemporary CLL therapies. We conducted an analysis of infectious outcomes in CLL patients who received IVIG between 2005 and 2022.

Methods:

This was a retrospective cohort study of CLL patients at a single institution. Patients who consented to CLL research were identified based on receipt of IVIG. Patients were excluded if they received IVIG for alternative indications (e.g., autoimmune hemolytic anemia). Infection frequency and severity were assessed during the year prior to and the year following IVIG initiation. Additional clinical parameters, including treatment history, concurrent therapy during IVIG use, and baseline immunoglobulin levels were also collected.

Results:

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, with an average time from CLL diagnosis to IVIG initiation of 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 levels 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). 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 in prior CLL treatment (75% vs. 83%, p = 0.57), baseline IgG (p = 0.91) or IgA levels (p = 0.93) were observed between patients with and without post-IVIG infections.

Conclusion:

In this intra-patient pre/post analysis, IVIG prophylaxis significantly reduced both moderate (grade 2 or higher) infections, consistent with prior literature. While IVIG is recommended primarily for patients with severe infections (per 2025 NCCN guidelines), our findings suggest IVIG may also yield meaningful improvements in patient quality of life by reducing grade 2 infections. Future IVIG studies should incorporate quality of life metrics to define the role of IVIG in modern CLL care.

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2025
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