Patients With B-Cell Cancers Have History of Increased Antimicrobial Use

A study published in the British Journal of Cancer shows that patients diagnosed with B-cell cancers had increased use of antimicrobials years before their diagnosis.¹

B-cell malignancies include a large, heterogeneous group of lymphoproliferative disorders such as follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL), which are slow-growing indolent non-Hodgkin lymphomas, and more aggressive types such as diffuse large B-cell lymphoma (DLBCL).² They are typically accompanied by immune dysfunction and are associated with an increased risk of infection. Patients diagnosed with CLL were found to have an increased use of antimicrobials and hence an increased risk of infections.¹ This study sought to find whether similar findings were seen in Danish patients with other B-cell malignancies—DLBCL, multiple myeloma (MM), FL, marginal zone lymphoma (MZL), and lymphoplasmacytic lymphoma (LPL).

Patients who were diagnosed with CLL, MM, MZL, and LPL demonstrated increased antimicrobial use for at least a decade before their diagnosis. | Image Credit: © Vitalii Vodolazskyi - stock.adobe.com

The study involved 2 cohorts: a population cohort with 30,389 participants, which was assembled using nationwide population and cancer registers, and a clinical cohort with 18,560 participants, which used the data from nationwide clinical quality registers and provided information on International indices and other detailed information. Cohorts were followed from 1996 or their date of birth (whichever came first) until their diagnosis of B-cell malignancy. A total of
435,846 controls were followed until their pseudo-diagnosis.

Patients who were diagnosed with CLL, MM, MZL, and LPL demonstrated increased antimicrobial use for at least a decade before their diagnosis. This increased antimicrobial use exceeded that of the controls. In contrast, patients diagnosed with FL had antimicrobial use that matched their controls until the year before their diagnosis. Patients with DLBCL had an increased use of antimicrobials in the year before diagnosis. The most commonly used antimicrobials were penicillins followed by macrolides. Patients diagnosed with CLL had increased HRs of macrolide and antiviral prescriptions for more than a decade before diagnosis. A similar finding was noted for patients with DLBCL.

The researchers also noted 3 different patterns of prediagnostic infections in the years before the last year leading to diagnosis. The first pattern was seen in patients diagnosed with CLL, LPL, MM, and MZL; their risk of infections had gradually increased over a decade or more. This pattern points toward a continuous deterioration of the immune system possibly due to the developing malignancy. It has been previously observed that precursors of CLL, LPL, and MM were associated with an increased risk of infection. MZL has been associated with specific autoimmune and specific chronic conditions.

The second pattern was seen in patients diagnosed with DLBCL. These patients had a 10% increased risk of infections for up to 15 years before increasing the use of antimicrobials. Immunodeficiencies such as AIDS and organ transplants have been associated with a risk of DLBCL. Patients were also seen to have elevated levels of serological markers of immune activation more than 7.5 years before diagnosis. The researchers speculate that immunodeficiency progresses to DLBCL due to the failure to eradicate malignant cells and curb oncogenic infections and the continuous immune stimulation due to recurrent infections.

A third pattern of prediagnostic infections was seen in patients who developed FL who had similar use of antimicrobials as their controls until a year before their diagnosis. Unlike other B-cell malignancies, immune deficiency does not indicate a risk for FL.

The researchers state a few limitations to this study. They say that symptoms of B cell malignancy may be misdiagnosed as a routine infection and hence be treated as an infection, and some newly diagnosed patients with lymphoma and MM show an elevated level of C-reactive protein. Therefore, some antimicrobial prescriptions may be a sign of early malignancy instead of a true infection. The study also did not adjust their results for comorbidities.

References
1. Packness E, Davidsson OB, Rostgaard K, et al. Infections and their prognostic significance before diagnosis of chronic lymphocytic leukemia, non-Hodgkin lymphoma, or multiple myeloma. Br J Cancer. Published online August 22, 2024. doi:10.1038/s41416-024-02816-2

2. Salles G, Barrett M, Foà R, et al. Rituximab in B-Cell hematologic malignancies: A review of 20 years of clinical experience. Adv Ther. 2017;34(10):2232-2273. doi:10.1007/s12325-017-0612-x