IgRT in Patients With CLL, NHL Associated With Lower Odds of Infections and Associated Antimicrobial Use

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Patients with blood cancers such as chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphomas (NHLs) are at a high risk for potentially life-threatening infections resulting from low immunoglobulin levels in the blood. According to authors who published their research in Blood Advances, patients who have CLL and NHL who received frequent tests for immunoglobulin G (IgG) were less likely to experience severe infections compared with those who were not frequently tested.

Immunoglobulins are proteins that assist the immune system when fighting off infections, and as many as 50% of patients with CLL and approximately 33% or patients with NHL die because of complications related to infections. Prior research, according to the study authors, demonstrated that immunoglobulin replacement therapy (IgRT) can reduce both recurrent and severe infections and potentially save patients’ lives.¹

For the retrospective, longitudinal study, investigators evaluated the patterns of IgG testing and the efficacy of IgRT in real-world adult patients with CLL or NHL. According to the authors, the study is the first large, real-world study to examine current IgG testing practices and the use of IgRT among patients who have CLL or NHL. A total of 17,192 patients were enrolled, of which 13,232 had NHL and the remaining 3960 had CLL. The median ages of patients with CLL and NHL were 68 and 64 years, respectively. Clinical data were collected from the Massachusetts General Brigham Research Patient Data Registry. Additionally, IgG testing, infections, and antimicrobial use were compared prior to IgRT initiation and again at the 3-, 6-, and 12-month periods following treatment, and the median patient follow-up was 4.5 years.^1,2

“Within each disease cohort, patients with 3 or more IgG tests were more likely to have low IgG detected and also more likely to receive IgRT,” said lead study investigator Jacob D. Soumerai, MD, assistant professor of medicine at Massachusetts General Hospital Cancer Center and Harvard Medical School, in a news release. “These findings suggest that patients known to have low levels of IgG might be more likely to communicate recurrent minor infections to their hematologists, leading to improved IgRT use.”¹

Approximately 67% (n = 2652) of patients in the CLL cohort had IgG testing and 6.5% (n = 259) received IgRT. In the NHL cohort, 51.2% (n = 6773) had IgG testing and 4.7% (n = 623) received IgRT. In patients who received IgRT, the median IgG levels were significantly higher, corresponding to a lower proportion of patients who had hypogammaglobulinemia at the 3-month mark post-initiation, compared with the 3-month mark prior to initiation.²

In the CLL subpopulation who received IgRT, the median IgG levels at 3, 6, and 12 months post index were 494, 491, and 499 mg/dL, respectively, and pre-index were 342.5, 355, and 359 mg/dL, respectively. Further, the prevalence of hypogammaglobulinemia was lower at all 3 follow-up periods (3 months: 65.6% vs 85.4%; 6 months: 62.7% vs 84.7%; and 12 months: 64.0% vs 81.6%). The NHL IgRT subpopulation had similar findings, with median IgG levels at 3, 6, and 12 months post-index being 521, 507, and 507 mg/dL, respectively, compared with the pre-index levels of 33.7, 346.5, and 552 mg/dL, respectively. The prevalence of hypogammaglobulinemia was also lower following IgRT initiation (3 months: 61.9% vs. 85.4%; 6 months: 68.0% vs. 85.2%; and 12 months: 70.7% vs. 84.0%).^1,2

Further, patients who received IgRT also had fewer infections and required fewer antimicrobial medications. In patients with CLL, IgRT initiation was associated with lower odds of infection and severe infection at 3 months after initiation vs 3 months prior to initiation (infection: OR [95% CI] = 0.52 [0.38–0.71], P<.0001]; severe infection: 0.48 [0.35–0.67], P < .0001]), and the same trend was observed in patients with NHL receiving IgRT (initiation (infection: OR [95% CI] = 0.60 [0.49–0.75], P < .0001); severe infection: 0.40 [0.32–0.50], P < .0001). In addition, both subpopulations had lower odds of sinopulmonary and skin or soft tissue infections, infection-associated antimicrobial use, and severe infection-associated antimicrobial use in the 3 months after compared with 3 months before the index date. The findings were also consistent for both groups at the 6- and 12-month follow-up periods.²

“Our most striking finding is that real-world practice is highly variable. We found that many patients are not tested for IgG deficiency, and IgRT is often not given despite the development of recurrent infections,” said Soumerai in the news release.¹

The investigators acknowledge that although clinical guidelines from multiple medical societies tend to recommend IgG testing for patients with NHL and CLL, specific recommendations that outline when and how often patients should be tested are inconsistent. Additionally, the investigators note that in both patient groups, the number of IgG tests per patient spanned a wide range, and many patients did not receive any IgG testing during the study’s duration.¹

“This underlines the urgent need to establish clear consensus on best practices for IgG testing and IgRT use in patients with CLL and NHL, to reduce recurrent infections in our patients,” concluded Soumerai in the news release.¹

References

1. American Society of Hematology. Reduced infections seen in CLL and NHL patients undergoing immunoglobulin testing and replacement therapy. News release. June 21, 2024. Accessed June 21, 2024. https://www.eurekalert.org/news-releases/1048703

2. Soumerai, JD, Yousif, Z, Gift, T, et al. IgG Testing, Immunoglobulin Replacement Therapy, and Infection Outcomes in Patients with CLL or NHL: Real-World Evidence. Blood Adv 2024; doi:10.1182/bloodadvances.2024013073