Immunoglobulin G Testing May Reduce Infections, Increase Receipt of Immunoglobulin Replacement Therapy in Patients With CLL and NHL

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Patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) who undergo frequent immunoglobulin G testing may be less likely to experience severe infections than those who don’t undergo frequent testing, according to a recent study published by Soumerai et al in Blood Advances.


Patients with hematologic malignancies such as CLL and NHL are often at an elevated risk for potentially life-threatening infections as a result of low blood levels of immunoglobulins. Up to 50% of patients with CLL and about 33% of those with NHL may die from infection-related complications.

Prior research has demonstrated that immunoglobulin replacement therapy may reduce both recurrent and severe infections, potentially increasing survival rates.

“This is [one of] the first large, real-world studies to examine current practices in [immunoglobulin G] testing and the use of [immunoglobulin replacement therapy] among patients with CLL and NHL,” explained lead study author Jacob D. Soumerai, MD, Assistant Professor of Medicine at Massachusetts General Hospital Cancer Center and Harvard Medical School.

Study Methods and Results

In the recent study, the investigators used the Mass General Brigham Research Patient Data Registry to analyze the de-identified medical records of 17,192 adult patients treated for CLL (n = 3,920) or NHL (n = 13,232) at one of eight affiliated hospitals across the Boston area between 2010 and 2023. The median patient follow-up in the database was 4.5 years.

Compared with the patients who had NHL, the investigators discovered that 67% vs 51.2% of the patients with CLL underwent immunoglobulin G testing and 6.5% vs 4.7% of them received immunoglobulin replacement therapy. They found that the patients who received immunoglobulin replacement therapy experienced fewer infections, required fewer antimicrobial drugs, and had higher blood levels of immunoglobulin G following administration of the treatment.

“Our most striking finding is that real-world practice is highly variable. We found that many patients are not tested for [immunoglobulin G] deficiency, and [immunoglobulin replacement therapy] is often not given despite the development of recurrent infections,” stressed Dr. Soumerai.

Among patients who received at least one immunoglobulin G test, the investigators compared blood levels of immunoglobulin G, the proportion of patients with immunoglobulin G levels below 500 mg/dL—which was deemed low—the rate of infections, and the use of antimicrobial medications at 3, 6, and 12 months prior to and following initiation of immunoglobulin replacement therapy. The results were similar across patient subgroups—for instance, males vs females—type of hematologic malignancy, and type of treatment received.

Further, frequent immunoglobulin G testing was associated with a reduction in the subsequent development of severe infections. After adjusting for potential confounders, the patients with CLL and NHL who had three or more preceding immunoglobulin G tests had a respective 92% and 86% lower risk of later developing a severe infection.


“Within each disease cohort, patients with three or more [immunoglobulin G] tests were more likely to have low [immunoglobulin G] detected and also more likely to receive [immunoglobulin replacement therapy],” underscored Dr. Soumerai. “These findings suggest that patients known to have low levels of [immunoglobulin G] might be more likely to communicate recurrent minor infections to their hematologists, leading to improved [immunoglobulin replacement therapy] use,” he added.

The investigators reported that their study was limited in that it was retrospective, only included patients treated in the Mass General Brigham health-care system, and did not capture patients who may have received immunoglobulin replacement therapy outside of this network. Furthermore, most of the patients in the registry were White, thereby not fully representing the U.S. population.

Although clinical guidelines from various professional medical societies generally recommend immunoglobulin G testing, specific recommendations regarding when and how often patients should be tested vary widely. Additionally, immunoglobulin G testing practices may vary among hematologists caring for patients with CLL and NHL. In both patient cohorts, the number of immunoglobulin G tests per patient spanned a wide range—with many patients not receiving any testing during the study period.

“This underlines the urgent need to establish clear consensus on best practices for [immunoglobulin G] testing and [immunoglobulin replacement therapy] use in patients with CLL and NHL, to reduce recurrent infections in our patients,” Dr. Soumerai concluded.

Disclosure: The research in this study was funded by Takeda Pharmaceuticals USA. For full disclosures of the study authors, visit

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