BeEAM (Bendamustine, Etoposide, Cytarabine, Melphalan) Versus BEAM (Carmustine, Etoposide, Cytarabine, Melphalan) as Conditioning Regimen Before Autologous Haematopoietic Cell Transplantation: A Systematic Review and Meta-Analysis

Abstract

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard of care for selected patients with refractory/relapsed Hodgkin’s lymphoma (HL) or non-Hodgkin’s lymphoma (NHL), and it is also used as first-line clinical consolidation option for some aggressive NHL subtypes. Conditioning regimen prior to ASCT is one of the essential factors related with clinical outcomes post transplant. The conditioning regimen of carmustine, etoposide, cytarabine, and melphalan (BEAM) traditionally is considered the standard of care for patients with lymphoma who are eligible for transplantation. Replacement of carmustine with bendamustine (BeEAM) was described as an alternative conditioning regimen in the autograft setting for patients with lymphoma. Several studies have reported inconsistent clinical outcomes comparing BeEAM and BEAM. Therefore, in the lack of well-designed prospective comparative studies, the comparison of BeEAM versus BEAM is based on retrospective trials. To compare the clinical outcomes between BeEAM and BEAM, we performed a meta-analysis of 10 studies which compared the outcomes between BeEAM and BEAM in patients autografted for lymphoma disease (HL or NHL). We searched article titles and compared transplantation with BeEAM versus BEAM in MEDLINE (PubMed), Cochrane library, and EMBASE database. Here, we report the results of nine main endpoints in our meta-analysis comparing BeEAM and BEAM, including neutrophil engraftment (NE), platelet engraftment (PE), overall survival (OS), progression free survival (PFS), non-relapse mortality (NRM), relapse rate (RR), grade 3 mucositis, renal toxicity, and cardiotoxicity. We discovered that the BeEAM regimen was associated with a slightly better PFS [pooled odds ratio (OR) of 0.70, 95% confidence interval (CI), 0.52–0.94, P = 0.02], lower RR (0.49, 95% CI, 0.31–0.76, P = 0.002), higher mucositis (3.43, 95% CI, 2.29–5.16, P = 0.001), renal toxicity (4.49, 95% CI, 2.68–7.51, P = 0.001), and cardiotoxicity (1.88, 95% CI, 1.03–3.40, P = 0.03). We also discovered that the two groups had equivalent NE (pooled WMD –0.64, 95% CI, –1.46 to 0.18, P = 0.13), PE (pooled WMD –0.3, 95% CI, –1.68 to 2.28, P = 0.77), OS (0.73, 95% CI, 0.52–1.01, P = 0.07), and NRM (1.51, 95% CI, 0.76–2.98, P = 0.24). The results of this meta-analysis show that the BeEAM regimen is a viable alternative to BEAM. More prospective comparisons between BeEAM and BEAM are required.

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“…However, due to the severe toxicity associated with whole-body irradiation, HDIT has been phased out. Contemporary conditioning regimens largely rely on BEAM (carmustine, etoposide, cytarabine, melphalan), recognized as a medium-intensity conditioning strategy ( 89 ). Moreover, low-intensity, or non-myeloablative, regimens typically incorporate CY and ATG ( 90 ), with ongoing discussions about the optimal conditioning methodology.…”