SID Heightens Infection Risk in Patients With B-Cell Malignancies

A new report finds secondary immunodeficiency disease (SID) also increases the risk of mortality in patients with B-cell malignancies.

Patients with mature B-cell malignancies face a higher infection burden and shorter overall survival if they also have secondary immunodeficiency disease (SID), according to a new report.1

The study, which was based on more than 20,000 real-world cases, was published in Clinical Lymphoma, Myeloma & Leukemia.1

The disease process underlying mature B-cell malignancies, along with the effect of immunosuppressive anticancer treatments, can increase a patient’s risk of developing SID, explained corresponding author Csaba Siffel, MD, PhD, of Takeda Development Center Americas Inc., and colleagues. Patients who develop SID often experience “severe, recurrent, or persistent” infections, the authors wrote, which in many cases can lead to death.

Patient in a hospital bed with doctor | Image credit: Tyler Olson -

The disease process underlying mature B-cell malignancies, along with the effect of immunosuppressive anticancer treatments, can increase a patient’s risk of developing secondary immunodeficiency disease.

Image credit: Tyler Olson -

For instance, the authors pointed to research by the Mayo Clinic that found infection was the second leading cause of death in patients with chronic lymphocytic leukemia (CLL), behind only CLL progression. The investigators in one of the Mayo studies found that at a median follow-up of 6 years, of the 46% of patients who had died, they died due to disease progression, but 8% of patients died due to infections.2

Yet, despite the risk associated with SID and related infections, there is only minimal guidance available to help clinicians identify patients at the highest risk of SID, and the guidance that exists is routinely implemented, Siffel and colleagues wrote. One problem, they noted, is that there is no universally accepted definition for SID.

In an effort to expand the scientific understanding of the problem of SID in patients with mature B-cell malignancies, the investigators used a database of electronic health records and administrative claims to compare patients with mature B-cell malignancies with and without concomitant SID. The authors queried cases of adult patients with CLL, small lymphocytic leukemia (SLL), multiple myeloma, or non-Hodgkin lymphoma between 2015 and 2020. Those patients were split into 2 cohorts based on whether their medical records suggested SID or not. Patients with primary immunodeficiency diseases were excluded from the study.

The 2 databases used were the Humedica database (H-DB) and the Guardian Research Network (GRN) database. Those databases yielded 2,221 patients with SID and 19,141 patients without SID who were diagnosed with a mature B-cell lymphoma. Using a 12-month follow-up period, the investigators found that in both of the databases consulted, patients in the SID cohort had a higher mean number of infections, and a higher mean number of severe infections, than patients in the non-SID cohort, despite both groups having similar baseline characteristics.

In fact, the authors found the majority of patients with SID had at least 1 infection. 

“In the SID cohorts of the GRN database and H-DB, respectively, 62.2% and 63.4% of patients experienced at least 1 infection during 12 months of follow-up; 30.5% and 34.5% of patients, respectively, experienced at least 1 severe bacterial infection,” Siffel and colleagues said.

Bacterial infections were the most common type of infection, followed by viral infections. The authors also found that, in both databases, people with SID were more likely to have one all-cause hospitalization than those without SID.

Finally, at all time points studied, the investigators said patients with SID had a shorter overall survival than those without SID.

“Median times to mortality for patients who died in the SID cohorts were 16.3 and 11.6 months in the GRN database and H-DB, respectively, and 16.7 and 15.1 months in the no-SID cohorts,” they wrote.

The authors noted that immunoglobulin replacement therapy is sometimes used as a prophylactic or to manage recurrent infections in patients with SID. The current data sets did not have sufficient information to judge the benefits of immunoglobulin replacement, and so the authors said further studies are warranted to evaluate the potential benefits of the treatment.

Siffel and colleagues said they hope that by gaining a better understanding of the burden of infection among patients with mature B-cell malignancies, clinicians can get a better idea of which patients are most likely to eventually develop SIDs, which in turn could lead to the development of better guidelines and management of SID.


  1. Richter J, Davids MS, Anderson-Smits C, et al. Burden of infection in patients with and without secondary immunodeficiency disease following diagnosis of a mature B cell malignancy. Clin Lymphoma Myeloma Leuk. Published online April 10, 2024. doi:10.1016/j.clml.2024.04.002
  2. Strati P, Parikh SA, Chaffee KG, et al. Relationship between co-morbidities at diagnosis, survival and ultimate cause of death in patients with chronic lymphocytic leukaemia (CLL): a prospective cohort study. Br J Haematol. 2017;178(3):394-402. doi:10.1111/bjh.14785
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