Safety of bendamustine for the treatment of indolent non-Hodgkin lymphoma: a UK real-world experience

Shotton, Rohan; Broadbent, Rachel; Alchawaf, Alia; Mohamed, Mohamed Bakri; Gibb, Adam; Martinez-Calle, Nicolás; Fox, Christopher P.; Bishton, Mark; Pender, Alexandra; Gleeson, Mary; Cunningham, David; Davies, Andrew John; Yadollahi, Sina; Eyre, Toby A.; Collins, Graham P.; Djebbari, Faouzi; Kassam, Shireen; Garland, Paula; Watts, Emily; Osborne, Wendy; Townsend, Wiliam M.; Pocock, Rachael; Ahearne, Matthew J.; Miall, Fiona; Wang, Xin; Linton, Kim M.

Abstract

Bendamustine is among the most effective chemotherapeutics for indolent B-cell non- Hodgkin lymphomas (iNHL), but trial reports of significant toxicity, including opportunistic infections and excess deaths, led to prescriber warnings. We conducted a multicenter observational study evaluating bendamustine toxicity in real-world practice. Patients receiving at least 1 dose of bendamustine with/without rituximab (R) for iNHL were included. Demographics, lymphoma and treatment details, and grade 3 to 5 adverse events (AEs) were analyzed and correlated. In total, 323 patients were enrolled from 9 National Health Service hospitals. Most patients (96%) received bendamustine-R, and 46%, R maintenance. Overall, 21.7% experienced serious AEs (SAE) related to treatment, including infections in 12%, with absolute risk highest during induction (63%), maintenance (20%), and follow-up (17%) and the relative risk highest during maintenance (54%), induction (34%), and follow-up (28%). Toxicity led to permanent treatment discontinuation for 13% of patients, and 2.8% died of bendamustine-related infections (n = 5), myelodysplastic syndrome (n = 3), and cardiac disease (n = 1). More SAEs per patient were reported in patients with mantle cell lymphoma, poor preinduction performance status (PS), poor premaintenance PS, and abnormal preinduction total globulins and in those receiving growth factors. Use of antimicrobial prophylaxis was variable, and 3 of 10 opportunistic infections occurred despite prophylaxis. In this real-world analysis, bendamustine-related deaths and treatment discontinuation were similar to those of trial populations of younger, fitter patients. Poor PS, mantle cell histology, and maintenance R were potential risk factors. Infections, including late onset events, were the most common treatment-related SAE and cause of death, warranting extended antimicrobial prophylaxis and infectious surveillance, especially for maintenance-treated patients.

Citation

Shotton, R., Broadbent, R., Alchawaf, A., Mohamed, M. B., Gibb, A., Martinez-Calle, N., Fox, C. P., Bishton, M., Pender, A., Gleeson, M., Cunningham, D., Davies, A. J., Yadollahi, S., Eyre, T. A., Collins, G. P., Djebbari, F., Kassam, S., Garland, P., Watts, E., Osborne, W., …Linton, K. M. (2024). Safety of bendamustine for the treatment of indolent non-Hodgkin lymphoma: a UK real-world experience. Blood Advances, 8(4), 878-888. https://doi.org/10.1182/bloodadvances.2023011305

• Journal Article Type: Article
• Acceptance Date: Oct 18, 2023
• Online Publication Date: Nov 15, 2023
• Publication Date: Feb 27, 2024
• Deposit Date: Nov 22, 2023
• Publicly Available Date: Nov 22, 2023
• Journal: Blood Advances
• Electronic ISSN: 2473-9529
• Publisher: American Society of Hematology
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Issue: 4
• Pages: 878-888
• DOI: https://doi.org/10.1182/bloodadvances.2023011305
• Keywords: Hematology
• Public URL: https://nottingham-repository.worktribe.com/output/27592889
• Publisher URL: https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2023011305/498748/Safety-of-bendamustine-for-the-treatment-of