Infectious Complications Associated with Bendamustine Exposure in Patients with Indolent non-Hodgkin Lymphoma Open Access

Background. Bendamustine is an alkylating and antimetabolite chemotherapy agent increasingly used in the treatment of indolent non-Hodgkin lymphoma (nHL) due to its efficacy and comparatively favorable toxicity profile. However, it causes significant T-cell lymphopenia, which may increase infectious risk.

Methods. Using the SEER-Medicare database, we identified patients with indolent nHL (follicular, marginal zone, Waldenstrom, and small lymphocytic (SLL/CLL)) via ICD-9 and ICD-O-3 codes. Administration of bendamustine, other chemotherapy regimens, and antimicrobial prophylaxis was identified by NDC drug codes. Infectious outcomes after receipt of bendamustine or first chemotherapy for groups treated with and without bendamustine, respectively, were defined by ICD-9 codes. Multivariate Cox proportional hazard regression, adjusting for differences in baseline characteristics, was conducted to determine infectious risks associated with bendamustine.

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Results. We identified 10,659 patients with indolent nHL (67.3% follicular, 18.3% Waldenstrom, 11.9% SLL/CLL, and 2.6% marginal zone) from 2006 to 2013, of whom 14.8% received bendamustine. Patients treated with bendamustine had higher incidences of many bacterial, viral, and fungal infections (Fig. 1). Adjusting for age, gender, lymphoma subtype and stage, number of chemotherapy regimens received, and corticosteroid exposure, bendamustine exposure was associated with an increased risk of both common infections such as streptococcus (HR 1.43, 95% CI 1.13–1.83), bacterial pneumonia (HR 1.53, 95% CI 1.24–1.74) and sepsis (HR 1.61, 95% CI 1.41–1.83) and opportunistic infections such as Pneumocystis pneumonia (PCP) (HR 3.37, 95% CI 1.67–.80), cytomegalovirus (HR 2.49, 95% CI 1.27–4.89), varicella zoster virus (HR 1.68, 95% CI 1.40–2.02), and histoplasmosis (HR 5.72, 95% CI 2.06–15.90) (Fig. 2).

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Conclusion. Indolent nHL patients treated with bendamustine may be at higher risk of infection, particularly opportunistic infections such as Pneumocystis pneumonia and herpesvirus reactivation controlled by cell-mediated immunity. Further investigation into the immune effects of bendamustine and role of antimicrobial prophylaxis is needed in this population.

Disclosures. S. Koo, Wako Diagnostics: Grant Investigator, Research support.

Author notes