IVIG Cuts Grade 2 Infections by 67% in CLL

Monthly intravenous immunoglobulin (IVIG) therapy was associated with a two-thirds reduction in clinically significant infections among patients with chronic lymphocytic leukemia (CLL) and hypogammaglobulinemia, according to a single-center retrospective study published in Cancer Research Communications.¹ The findings add patient-level evidence to a debate about whether immunoglobulin replacement therapy (IgRT) meaningfully reduces infection burden in a disease population increasingly managed with targeted agents over traditional chemotherapy.

What Did the Pre- and Post-IVIG Data Show?

Investigators at UC San Diego reviewed outcomes for 52 patients with CLL who initiated IVIG between 2005 and 2022—their median overall start occurred in 2014—comparing infection rates in the 12 months before and after treatment started. All patients had experienced at least 1 Common Terminology Criteria for Adverse Events infection of grade 2 or higher—meaning an infection requiring oral antimicrobials or outpatient management—in the year prior to IVIG initiation, with a mean of 2.1 infections per patient.

Following the start of IVIG, dosed at 0.4 g/kg every 28 days per National Comprehensive Cancer Network guidelines, only 17 patients (33%) experienced a grade 2 or higher infection, and the mean per-patient count dropped to 0.4. The relative risk (RR) reduction was 67% (RR, 0.33; 95% CI, 0.22-0.48; P < .0001), with an absolute risk reduction of 67% and a number needed to treat of 1.5—with the authors highlighting this final result as evidence of meaningful clinical impact at the individual patient level. Grade 3 infections requiring hospitalization or intravenous antimicrobials fell from 4 patients (8%) in the pre-IVIG year to 2 patients (4%) in the follow-up year, although the authors caution that these events were too infrequent to support strong conclusions.

Who Was Most Affected, and What Did Not Predict Residual Infections?

The median patient age at IVIG initiation was 68 years, with a mean interval of 9.3 years from CLL diagnosis; the median (IQR) age at diagnosis was 58 years (52-64). Mean baseline immunoglobulin G (IgG) was 389 mg/dL (range, 93-891), and 75% of patients fell below the 500-mg/dL threshold commonly used to guide IgRT initiation; the remaining 13 were started on IVIG based on clinical concern for immune dysfunction and recurrent infections despite marginally higher IgG levels. Seventy-seven percent had received prior or concurrent CLL-directed therapy.

Importantly, baseline IgG (P = .79) and IgA levels (P = .22), along with recent CLL treatment (P = .91), were not statistically significant predictors of whether a patient went on to experience post-IVIG infections. The trough IgG level among patients who did develop infections after IVIG, which was a median of 703 mg/dL, was comparable to that of those who remained free of infection (median, 687 mg/dL), suggesting that achieving a target IgG level alone does not fully explain protection from infection. The authors note that hypogammaglobulinemia addresses only 1 component of the broad immune dysfunction that characterizes CLL.

How Do These Findings Fit the Evolving Evidence Base?

These results contrast with a previous large real-world analysis that did not show that patients with CLL who received regular IgRT had reduced serious infection–related hospitalizations.² That study found serious infections clustered around periods of IgRT initiation, reinitiation, and discontinuation. The authors of the current study contend that their approach of continuous monthly IVIG, combined with granular chart-level review of lower-grade infections, may explain the divergent findings, and they recommend that prospective IVIG studies incorporate patient-reported quality-of-life instruments to capture these burdens, which are not well reflected in hospitalization-based end points.¹

Cost-effectiveness also remains an unresolved issue, with previous research raising concerns about high IVIG treatment costs relative to clinical benefit.³ However, with a number needed to treat of 1.5, the present authors argue that identifying which subgroups benefit most could allow for more targeted and cost-effective deployment of IgRT.¹

What Comes Next for IgRT in CLL?

The study’s retrospective design, single-center setting, and study period predating widespread adoption of Bruton tyrosine kinase inhibitors and venetoclax limit its generalizability. Also, with the median year of IVIG initiation being 2014, most patients were not on contemporary targeted agents when they began IgRT. The authors acknowledge they could not evaluate outcomes following IVIG discontinuation, nor could they control for COVID-19–related changes in infection patterns during the later study period.

Nonetheless, the findings reinforce existing NCCN guidance supporting IgRT in patients with CLL who have recurrent infections and low serum IgG, while also suggesting that patients with IgG levels modestly above the 500 mg/dL threshold may still benefit if their infection burden is high.

“Hypogammaglobulinemia and recurrent infections remain a complication of CLL, despite contemporary agents,” the authors concluded. “IVIG may be an effective supportive-care strategy in patients with CLL.”

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 Commun. 2026;6(5):1146-1150. doi:10.1158/2767-9764.CRC-26-0177
2. Shaw ML. Immunoglobulin therapy may not reduce infection risk in CLL. AJMC^®. February 16, 2026. Accessed May 28, 2026. https://www.ajmc.com/view/immunoglobulin-therapy-may-not-reduce-infection-risk-in-cll
3. Weeks JC, Tierney MR, Weinstein MC. Cost effectiveness of prophylactic intravenous immune globulin in chronic lymphocytic leukemia. N Engl J Med. 1991;325(2):81-86. doi:10.1056/NEJM199107113250202