Despite benefits, many patients with leukemia, lymphoma do not undergo IgG tests
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Many patients with chronic lymphocytic leukemia or non-Hodgkin lymphoma do not undergo immunoglobulin G testing despite its potential to reduce likelihood of severe infections.
Blood cancers increase risk for life-threatening infections due to low blood levels of IgG, which play an essential role in combating infections. Up to half of patients with CLL and a third of those with NHL die of infection-related complications.
“We know that [for] well-selected patients, giving back immunoglobulin in the form of some sort of immunoglobulin replacement therapy can achieve lower rates of recurrent infections,” investigator Jacob D. Soumerai, MD, assistant professor of medicine at Massachusetts General Hospital Cancer Center and Harvard Medical School, told Healio.
Soumerai and colleagues conducted a retrospective longitudinal study to evaluate igG testing and effectiveness of immunoglobulin replacement therapy in a real-world population of patients with CLL or NHL.
Researchers assessed medical records of 17,192 adults receiving treatment for CLL (n = 3,920) or NHL (n =13,232) at one of eight Boston-area hospitals between 2010 and 2023.
After a median follow-up of 4.5 years, 51.2% of patients with NHL had undergone IgG testing and 4.7% received immunoglobulin replacement therapy, whereas 67% of those with CLL underwent IgG testing and 6.5% received Ig replacement therapy.
Increased frequency of IgG testing appeared associated with significantly reduced likelihood of severe infection.
In addition, among patients who initiated Ig replacement therapy, the percentage of those with low IgG levels, the odds for any infection or severe infection, and the use of antimicrobials decreased significantly.
“We need to be doing better at identifying patients who are at increased risk for recurrent and severe infections with hypogammaglobulinemia so we’re intervening when appropriate and not intervening when it’s not appropriate,” Soumerai said. “I also think we have a flawed system — we wait for infections before we administer a prophylactic to reduce infections. That’s an obvious area for improvement.”
Healio spoke with Soumerai about the findings and their implications.
Healio: Why did you conduct this study?
Soumerai: We have dramatically improved outcomes for patients with CLL or non-Hodgkin lymphoma. We have to do better reducing infection risk among these individuals.
There are different practices for how we screen for hypogammaglobulinemia, when we initiate Ig replacement therapy, and how we administer or deliver this treatment. This suggests some disconnect between guideline recommendations and routine care. Our goal was to define current real-world practice for IgG testing and Ig replacement therapy practices to better understand when and how this is administered.
Healio: Did anything surprise you?
Soumerai: Yes, the key unexpected finding for me was the relatively low rate of IgG testing. This is not a required test in the absence of recurrent or severe infections. We don’t need to universally monitor for IgG, but most guidelines recommend at least evaluating this at diagnosis. If a patient doesn’t have a history of infection at diagnosis, it’s reasonable to be conservative with testing. However, if you don’t check at diagnosis, I think you’re less likely to check it when patients return for subsequent visits. At those visits you’re going to be focused most on their lymphoma or CLL, so testing is not necessarily a priority.
One key conclusion is that there’s a lot of heterogeneity, and we need guidelines to make sure we’re doing right by these patients. National Comprehensive Cancer Network provides very clear guidance on this, but I think some sort of harmonization across guidelines and education would be helpful.
Healio: What are the next steps in research?
Soumerai: We are evaluating a tool a colleague developed called system serology. It goes beyond the IgG number, which does not necessarily tell you everything. I have patients with IgG levels of 50 mg/dL — which is extraordinarily low — who don’t have recurrent infections. I also have patients with levels of 500 mg/dL who are frequently infected, so there’s probably much more there than just the raw number.
My colleague developed a panel that identifies antibodies against 11 common pathogens that our patients with CLL face. We will evaluate this among 150 patients and follow them for 2 years to see who develops infections. We want to develop a tool to identify who is at risk for specific infections based on the presence or absence of antibodies. If there are antibodies present, we want to understand whether these antibodies are functional and able to clear infections.
We can do better by measuring IgG, taking a through history of prior infections and initiating Ig replacement therapy when clinically appropriate, However, the next step is to develop a more personalized approach, and I hope studies like this will enable us to do that.
References:
- American Society of Hematology. Reduced infections seen in CLL and NHL patients undergoing immunoglobulin testing and replacement therapy (press release). Available at: https://www.hematology.org/newsroom/press-releases/2024/reduced-infections-seen-in-cll-and-nhl-patients-undergoing-immunoglobin-testing. Published June 21, 2024. Accessed July 29, 2024.
- Soumerai JD, et al. Blood Adv. 2024;doi:10.1182/bloodadvances.2024013073.
For more information:
Jacob D. Soumerai, MD, can be reached at jsoumerai@mgh.harvard.edu.
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