BendaEAM versus BEAM as conditioning regimen for ASCT in patients with relapsed lymphoma (BEB): a multicentre, randomised, phase 2 trial.

Autologous stem cell transplantation BEAM Bendamustine Conditioning regimen Lymphoma

Journal

EClinicalMedicine
ISSN: 2589-5370
Titre abrégé: EClinicalMedicine
Pays: England
ID NLM: 101733727

Informations de publication

Date de publication:
Dec 2023
Historique:
received: 22 05 2023
revised: 23 10 2023
accepted: 31 10 2023
medline: 29 11 2023
pubmed: 29 11 2023
entrez: 29 11 2023
Statut: epublish

Résumé

Replacement of carmustine (BCNU) in the BEAM regimen (BCNU, etoposide, cytarabine, melphalan) with bendamustine (BendaEAM) before autologous stem cell transplantation (ASCT) is feasible in lymphoma. However, randomised trials are lacking. Here, we present the first trial addressing this topic. This multicentre, randomised, phase 2 study (BEB-trial) conducted at four haematological centres in Austria and Switzerland compares BEAM with BendaEAM in patients with relapsed lymphoma. Both regimens were administered intravenously before ASCT, in BEAM according to the standard protocol (300 mg/m Between April 20, 2015, and November 28, 2018, 108 patients were enrolled; of whom 53 were randomly assigned to receive BendaEAM (36 male, 17 female) and 55 to receive BEAM (39 male, 16 female). All patients engrafted rapidly. Lung toxicity did not differ between groups (BendaEAM: n = 8, 19.5%; BEAM: n = 11, 25.6%; risk difference = -6.1%: 95% confidence interval: -23.9% to 11.7%). Acute toxicities of at least grade 3 were comparable in both groups (BendaEAM: 35.8%, BEAM: 30.9%). Overall survival (BendaEAM: 92.5%, BEAM: 89.1%) and complete remission (BendaEAM: 76.7%, BEAM: 74.3%) after 1 year (median follow-up: 369 days) were similar. No difference in quality of life was observed. Results were similar for both regimens in terms of survival and response rates. A phase 3 non-inferiority study is required to investigate whether BendaEAM can be considered as an alternative to BEAM. Mundipharma.

Sections du résumé

Background UNASSIGNED
Replacement of carmustine (BCNU) in the BEAM regimen (BCNU, etoposide, cytarabine, melphalan) with bendamustine (BendaEAM) before autologous stem cell transplantation (ASCT) is feasible in lymphoma. However, randomised trials are lacking. Here, we present the first trial addressing this topic.
Methods UNASSIGNED
This multicentre, randomised, phase 2 study (BEB-trial) conducted at four haematological centres in Austria and Switzerland compares BEAM with BendaEAM in patients with relapsed lymphoma. Both regimens were administered intravenously before ASCT, in BEAM according to the standard protocol (300 mg/m
Findings UNASSIGNED
Between April 20, 2015, and November 28, 2018, 108 patients were enrolled; of whom 53 were randomly assigned to receive BendaEAM (36 male, 17 female) and 55 to receive BEAM (39 male, 16 female). All patients engrafted rapidly. Lung toxicity did not differ between groups (BendaEAM: n = 8, 19.5%; BEAM: n = 11, 25.6%; risk difference = -6.1%: 95% confidence interval: -23.9% to 11.7%). Acute toxicities of at least grade 3 were comparable in both groups (BendaEAM: 35.8%, BEAM: 30.9%). Overall survival (BendaEAM: 92.5%, BEAM: 89.1%) and complete remission (BendaEAM: 76.7%, BEAM: 74.3%) after 1 year (median follow-up: 369 days) were similar. No difference in quality of life was observed.
Interpretation UNASSIGNED
Results were similar for both regimens in terms of survival and response rates. A phase 3 non-inferiority study is required to investigate whether BendaEAM can be considered as an alternative to BEAM.
Funding UNASSIGNED
Mundipharma.

Identifiants

pubmed: 38024477
doi: 10.1016/j.eclinm.2023.102318
pii: S2589-5370(23)00495-9
pmc: PMC10679477
doi:

Banques de données

ClinicalTrials.gov
['NCT02278796']

Types de publication

Journal Article

Langues

eng

Pagination

102318

Informations de copyright

© 2023 Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

FK received research funding from Mundipharma and honoraria from Novartis, Gilead, Janssen, Astra Zeneca, Abbvie, Roche, Takeda, BMS, and Incyte. VB-A received honoraria from AOP Orphan, Incyte, Novartis, Gilead, BMS Celgene, Amgen, Takeda, Sanofi, GSK, and Janssen-Cilag. TN received honoraria from Janssen and Roche. RG received honoraria from Celgene, Novartis, Roche, BMS, Takeda, Abbvie, Astra Zeneca, Janssen-Cilag, MSD, Merck, Gilead, Daiichi Sankyo, Sanofi Amgen, and Sandoz; and holds stock (options) from Novo Nordisk and Lilly. ABe received honoraria from Roche. All other authors declare no competing interests.

Références

Eur J Cancer. 2009 Jan;45(2):228-47
pubmed: 19097774
J Clin Oncol. 2014 Sep 20;32(27):3059-68
pubmed: 25113753
Kidney Int. 2011 Jun;79(12):1341-52
pubmed: 21307840
Eur J Haematol. 2018 Sep;101(3):326-331
pubmed: 29799642
Bone Marrow Transplant. 2016 Feb;51(2):319-21
pubmed: 26524266
Cell Transplant. 2023 Jan-Dec;32:9636897231179364
pubmed: 37350429
Am J Hematol. 2016 May;91(5):E296
pubmed: 26840242
Blood. 2011 Sep 22;118(12):3419-25
pubmed: 21816830
Transplant Cell Ther. 2023 Jan;29(1):34.e1-34.e7
pubmed: 36243319
Br J Haematol. 2019 Jul;186(2):234-242
pubmed: 30980398
Contemp Oncol (Pozn). 2018;22(2):113-117
pubmed: 30150889
Ann Oncol. 2004 Aug;15(8):1250-5
pubmed: 15277266
Bone Marrow Transplant. 2022 Apr;57(4):627-632
pubmed: 35149851
Clin Lymphoma Myeloma Leuk. 2020 Jun;20(6):371-376.e1
pubmed: 32151585
Pediatr Radiol. 2018 Dec;48(13):1875-1883
pubmed: 30121852
Semin Oncol. 2002 Aug;29(4 Suppl 13):12-4
pubmed: 12170426
Am J Hematol. 2018 Jun;93(6):729-735
pubmed: 29473209
Br J Haematol. 2021 Feb;192(3):e94-e98
pubmed: 33421031
Haematologica. 2022 May 01;107(5):1045-1053
pubmed: 34382386
J Natl Cancer Inst. 1993 Mar 3;85(5):365-76
pubmed: 8433390
Am J Respir Crit Care Med. 2000 Jan;161(1):17-25
pubmed: 10619792
Bone Marrow Transplant. 2019 Dec;54(12):1923-1925
pubmed: 30890768
J Clin Oncol. 2022 Jun 20;40(18):1991-2003
pubmed: 35263165
Clin Cancer Res. 2008 Jan 1;14(1):309-17
pubmed: 18172283
J Clin Oncol. 1995 Mar;13(3):588-95
pubmed: 7884420
J Clin Oncol. 2010 Sep 20;28(27):4184-90
pubmed: 20660832
Blood Adv. 2021 Nov 9;5(21):4327-4337
pubmed: 34610094
N Engl J Med. 1995 Dec 7;333(23):1540-5
pubmed: 7477169
Bone Marrow Transplant. 1996 Mar;17(3):335-40
pubmed: 8704683
Sci Rep. 2021 Jul 7;11(1):14071
pubmed: 34234243
Blood. 2022 Mar 3;139(9):1330-1339
pubmed: 34570879
Bone Marrow Transplant. 2000 Feb;25(3):309-13
pubmed: 10673703
Cancer. 2002 Jan 15;94(2):452-8
pubmed: 11900231
Blood. 2005 Jun 1;105(11):4215-22
pubmed: 15701723
Bone Marrow Transplant. 2021 Jul;56(7):1651-1664
pubmed: 33623153

Auteurs

Felix Keil (F)

3rd Medical Department for Haematology and Oncology, Hanusch Hospital, Vienna, Austria.

Antonia M S Müller (AMS)

Department of Transfusion Medicine and Cell Therapy, Medical University of Vienna, Vienna, Austria.
Department of Medical Oncology and Haematology, University Hospital Zurich, Zurich, Switzerland.

Andrea Berghold (A)

Institute for Medical Informatics, Statistics, and Documentation, Medical University Graz, Graz, Austria.

Regina Riedl (R)

Institute for Medical Informatics, Statistics, and Documentation, Medical University Graz, Graz, Austria.

Veronika Buxhofer-Ausch (V)

Department of Internal Medicine I with Haematology, Stem Cell Transplantation, Haemostaseology and Medical Oncology, Ordensklinikum Linz Elisabethinen, Linz, Austria.
Medical Faculty, Johannes Kepler University Linz, Linz, Austria.

Judith Schuster (J)

Austrian Group Medical Tumor Therapy (AGMT), Salzburg, Austria.

Corinne Vorburger (C)

Department of Medical Oncology, Inselspital, Bern University Hospital, Bern, Switzerland.

Alexandra Böhm (A)

Haematological Health Care Centre of the ÖGK Mariahilf, Vienna, Austria.

Michael Panny (M)

3rd Medical Department for Haematology and Oncology, Hanusch Hospital, Vienna, Austria.

Thomas Nösslinger (T)

3rd Medical Department for Haematology and Oncology, Hanusch Hospital, Vienna, Austria.

Richard Greil (R)

Austrian Group Medical Tumor Therapy (AGMT), Salzburg, Austria.
Cancer Cluster Salzburg (CCS), Salzburg, Austria.
III Medical Department with Haematology and Medical Oncology, Haemostaseology, Rheumatology and Infectious Diseases, Oncologic Centre, Paracelsus Medical University, Salzburg, Austria.
Salzburg Cancer Research Institute with Laboratory of Immunological and Molecular Cancer Research and Centre for Clinical Cancer and Immunology Trials (CCCIT), Salzburg, Austria.

Panagiotis Samaras (P)

Clinic for Haematology and Oncology Hirslanden Zurich, Zurich, Switzerland.

Celine Bencker (C)

3rd Medical Department for Haematology and Oncology, Hanusch Hospital, Vienna, Austria.

Markus Rütti (M)

Department of Medical Oncology and Haematology, University Hospital Zurich, Zurich, Switzerland.

Thomas Pabst (T)

Department of Medical Oncology, Inselspital, Bern University Hospital, Bern, Switzerland.

Classifications MeSH