PMID- 37967358
OWN - NLM
STAT- MEDLINE
DCOM- 20240216
LR  - 20240221
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 8
IP  - 4
DP  - 2024 Feb 27
TI  - Safety of bendamustine for the treatment of indolent non-Hodgkin lymphoma: a UK 
      real-world experience.
PG  - 878-888
LID - 10.1182/bloodadvances.2023011305 [doi]
AB  - 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.
CI  - (c) 2024 by The American Society of Hematology. Licensed under Creative Commons 
      Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), 
      permitting only noncommercial, nonderivative use with attribution. All other 
      rights reserved.
FAU - Shotton, Rohan
AU  - Shotton R
AUID- ORCID: 0000-0003-4545-8296
AD  - The Christie NHS Foundation Trust, Manchester, United Kingdom.
FAU - Broadbent, Rachel
AU  - Broadbent R
AD  - The Christie NHS Foundation Trust, Manchester, United Kingdom.
FAU - Alchawaf, Alia
AU  - Alchawaf A
AD  - The Christie NHS Foundation Trust, Manchester, United Kingdom.
FAU - Mohamed, Mohamed Bakri
AU  - Mohamed MB
AUID- ORCID: 0000-0003-0179-9806
AD  - The Christie NHS Foundation Trust, Manchester, United Kingdom.
FAU - Gibb, Adam
AU  - Gibb A
AD  - The Christie NHS Foundation Trust, Manchester, United Kingdom.
FAU - Martinez-Calle, Nicolas
AU  - Martinez-Calle N
AUID- ORCID: 0000-0002-5184-9464
AD  - Clinical Haematology, Nottingham University Hospitals NHS Trust, Nottingham, 
      United Kingdom.
FAU - Fox, Christopher P
AU  - Fox CP
AUID- ORCID: 0000-0002-6322-9254
AD  - Clinical Haematology, Nottingham University Hospitals NHS Trust, Nottingham, 
      United Kingdom.
AD  - School of Medicine, University of Nottingham, Nottingham, United Kingdom.
FAU - Bishton, Mark
AU  - Bishton M
AD  - Clinical Haematology, Nottingham University Hospitals NHS Trust, Nottingham, 
      United Kingdom.
FAU - Pender, Alexandra
AU  - Pender A
AUID- ORCID: 0000-0001-5912-2457
AD  - Department of Medicine, The Royal Marsden Hospital, London, United Kingdom.
FAU - Gleeson, Mary
AU  - Gleeson M
AD  - Haematology, The Royal Marsden Hospital, London, United Kingdom.
FAU - Cunningham, David
AU  - Cunningham D
AUID- ORCID: 0000-0001-5158-1069
AD  - Haematology, The Royal Marsden Hospital, London, United Kingdom.
FAU - Davies, Andrew
AU  - Davies A
AUID- ORCID: 0000-0002-7517-6938
AD  - Cancer Research UK/NIHE Experimental Cancer Medicines Centre, University of 
      Southampton, Southampton, United Kingdom.
FAU - Yadollahi, Sina
AU  - Yadollahi S
AD  - Haematology, Haematology and Cancer Centre, Oxford University Hospitals NHS 
      Foundation Trust, Oxford, United Kingdom.
FAU - Eyre, Toby A
AU  - Eyre TA
AUID- ORCID: 0000-0002-6631-9749
AD  - Haematology, Haematology and Cancer Centre, Oxford University Hospitals NHS 
      Foundation Trust, Oxford, United Kingdom.
FAU - Collins, Graham
AU  - Collins G
AD  - Haematology, Haematology and Cancer Centre, Oxford University Hospitals NHS 
      Foundation Trust, Oxford, United Kingdom.
FAU - Djebbari, Faouzi
AU  - Djebbari F
AD  - Haematology, Haematology and Cancer Centre, Oxford University Hospitals NHS 
      Foundation Trust, Oxford, United Kingdom.
FAU - Kassam, Shireen
AU  - Kassam S
AD  - Haematology, King's College Hospital, London, United Kingdom.
FAU - Garland, Paula
AU  - Garland P
AD  - Haematology, King's College Hospital, Princess Royal Site, Kent, United Kingdom.
FAU - Watts, Emily
AU  - Watts E
AD  - Haematology, Freeman Hospital, Newcastle, United Kingdom.
FAU - Osborne, Wendy
AU  - Osborne W
AD  - Haematology, Freeman Hospital, Newcastle, United Kingdom.
FAU - Townsend, William
AU  - Townsend W
AUID- ORCID: 0000-0003-3975-2448
AD  - Haematology, University College Hospital London, London, United Kingdom.
FAU - Pocock, Rachael
AU  - Pocock R
AD  - Haematology, University College Hospital London, London, United Kingdom.
FAU - Ahearne, Matthew J
AU  - Ahearne MJ
AUID- ORCID: 0000-0002-2037-3926
AD  - Haematology, University Hospitals of Leicester NHS Trust, Leicester, United 
      Kingdom.
FAU - Miall, Fiona
AU  - Miall F
AD  - Haematology, University Hospitals of Leicester NHS Trust, Leicester, United 
      Kingdom.
FAU - Wang, Xin
AU  - Wang X
AUID- ORCID: 0000-0001-5192-8093
AD  - Statistics Group, Clinical Outcome Unit, Digital Services, The Christie NHS 
      Foundation Trust, Manchester, United Kingdom.
FAU - Linton, Kim M
AU  - Linton KM
AUID- ORCID: 0000-0002-3294-1548
AD  - The Christie NHS Foundation Trust, Manchester, United Kingdom.
AD  - Division of Cancer Sciences, The University of Manchester, Manchester, United 
      Kingdom.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Observational Study
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
RN  - 981Y8SX18M (Bendamustine Hydrochloride)
RN  - 0 (Anti-Infective Agents)
SB  - IM
MH  - Humans
MH  - Adult
MH  - Bendamustine Hydrochloride/adverse effects
MH  - State Medicine
MH  - *Lymphoma, Non-Hodgkin/drug therapy
MH  - *Lymphoma, Mantle-Cell/drug therapy
MH  - *Lymphoma, B-Cell/drug therapy
MH  - *Anti-Infective Agents/therapeutic use
MH  - *Opportunistic Infections/chemically induced/drug therapy
MH  - United Kingdom
PMC - PMC10875258
COIS- Conflict-of-interest disclosure: N.M.-C. received honoraria from Janssen; 
      received travel support and honoraria from and served on the advisory board of 
      AbbVie; received travel support and honoraria from AstraZeneca; and served on the 
      advisory board of and received honoraria from Takeda. C.P.F. consults and 
      performs educational activities for AbbVie, AstraZeneca, Atara Biotherapeutics, 
      Celgene/Bristol Myers Squibb, Genmab, Gilead/Kite, Incyte, Janssen, Lilly, 
      MorphoSys, Ono, Roche, and Takeda, and received research funding from BeiGene. 
      A.D. serves on the advisory board of and received research funding, honoraria, 
      and travel fees for scientific conferences from Celgene and Roche; serves on the 
      advisory board of and received research support and honoraria from Kite; serves 
      on the advisory board of and received research support from Karyopharm 
      Therapeutics; received research support and honoraria from Acerta 
      Pharma/AstraZeneca and ADC Therapeutics; serves on the advisory board of Incyte; 
      received research support from Merck Sharp & Dohme (MSD); and serves on the 
      advisory board of AbbVie. T.A.E. reports education and advisory board honoraria, 
      and scientific conference travel support from Roche; reports honoraria and 
      research and scientific conference travel support from Gilead; reports education 
      and advisory board honoraria from Kite; reports honoraria from Janssen; reports 
      honoraria and scientific conference travel support from AbbVie; received 
      honoraria, research funding, and scientific conference travel support from 
      AstraZeneca; received advisory board honoraria from, and served on the steering 
      committee of, Loxo Oncology; received advisory board honoraria and research 
      funding from BeiGene; and received advisory board honoraria from Incyte and 
      Secura Bio. W.O. reports speaker honoraria from Roche, Takeda, Pfizer, Kite 
      Gilead, AstraZeneca, Novartis, Kyowa Kirin, Incyte, and Janssen; serving on 
      advisory boards for Roche, Servier, Takeda, MSD, Kite Gilead, Novartis, Beigine, 
      Autolus, Kyowa Kirin, Incyte, Sobi, Janssen, and Synoes; and support for medical 
      education from Novartis, Takeda, and Roche. W.T. has received honoraria, 
      speaker's fees, and travel support to international conferences from Roche, 
      Takeda, Incyte, and Gilead. The remaining authors declare no competing financial 
      interests.
EDAT- 2023/11/15 18:42
MHDA- 2024/02/16 06:43
PMCR- 2023/11/17
CRDT- 2023/11/15 16:33
PHST- 2023/10/18 00:00 [accepted]
PHST- 2023/07/26 00:00 [received]
PHST- 2024/02/16 06:43 [medline]
PHST- 2023/11/15 18:42 [pubmed]
PHST- 2023/11/15 16:33 [entrez]
PHST- 2023/11/17 00:00 [pmc-release]
AID - 498748 [pii]
AID - 10.1182/bloodadvances.2023011305 [doi]
PST - ppublish
SO  - Blood Adv. 2024 Feb 27;8(4):878-888. doi: 10.1182/bloodadvances.2023011305.