A Comparison of the Conditioning Regimens BEAM and FEAM for Autologous Hematopoietic Stem Cell Transplantation in Lymphoma: An Observational Study on 1038 Patients From Fondazione Italiana Linfomi

Abstract

BEAM (carmustine [bis-chloroethylnitrosourea (BCNU)]-etoposide-cytarabine-melphalan) chemotherapy is the standard conditioning regimen for autologous stem cell transplantation (ASCT) in lymphomas. Owing to BCNU shortages, many centers switched to fotemustine-substituted BEAM (FEAM), lacking proof of equivalence. We conducted a retrospective cohort study in 18 Italian centers to compare the safety and efficacy of BEAM and FEAM regimens for ASCT in lymphomas performed from 2008 to 2015. We enrolled 1038 patients (BEAM = 607, FEAM = 431), of which 27% had Hodgkin lymphoma (HL), 14% indolent non-Hodgkin lymphoma (NHL), and 59% aggressive NHL. Baseline characteristics including age, sex, stage, B-symptoms, extranodal involvement, previous treatments, response before ASCT, and overall conditioning intensity were well balanced between BEAM and FEAM; notable exceptions were median ASCT year (BEAM = 2011 versus FEAM = 2013, P < .001), Sorror score ≥3 (BEAM = 15% versus FEAM = 10%, P = .017), and radiotherapy use (BEAM = 18% versus FEAM = 10%, P < .001). FEAM conditioning resulted in higher rates of gastrointestinal and infectious toxicities, including severe oral mucositis grade ≥3 (BEAM = 31% versus FEAM = 44%, P < .001), and sepsis from Gram-negative bacteria (mean isolates/patient: BEAM = .1 versus FEAM = .19, P < .001). Response status at day 100 post-ASCT (overall response: BEAM = 91% versus FEAM = 88%, P = .42), 2-year overall survival (83.9%; 95% confidence interval [CI], 81.5% to 86.1%) and progression-free survival (70.3%; 95% CI, 67.4% to 73.1%) were not different in the two groups. Mortality from infection was higher in the FEAM group (subhazard ratio, 1.99; 95% CI, 1.02 to 3.88; P = .04). BEAM and FEAM do not appear different in terms of survival and disease control. However, due to concerns of higher toxicity, fotemustine substitution in BEAM does not seem justified, if not for easier supply.

Gemcitabine‐based conditioning compared to BEAM/BEAC conditioning prior to autologous stem cell transplantation for non‐Hodgkin lymphoma: No difference in outcomes

“…Some studies have suggested that BEAC may increase the risk of cardiotoxicity 23,24 ; however, a recent large-scale retrospective matched cohort study by the European Society for Blood and Marrow Transplantation (EBMT) found comparable outcomes and toxicity profiles for ASCT conditioned with BEAM or BEAC. 15 In line with previous literature, 9,15,24 the most prevalent grade 3/4 extrahematologic toxicities in our BEAM/BEAC group were nausea/vomiting (20.7%), mucositis (14.1%), and diarrhea (13.0%). Regarding the GBM regimen, Nieto et al reported that the most common ≥grade 3 adverse events in r/r lymphoma and multiple myeloma were mucositis (27%-41%), dermatitis (7%-10%), hyperbilirubinemia (12%-19%), and elevated transaminases (9%-19%).…”

“…Recent decades, however, have seen a limited availability of melphalan, leading to the emergence of alternative conditioning regimens, such as BEAC (which substitutes cyclophosphamide for melphalan), with reports indicating comparable toxicities and outcomes 13–15 . After 2010, a shortage of BCNU prompted the exploration of alternatives like bendamustine or formustine, which, while clinically effective, are associated with new adverse effects, including renal injury 9,16,17 . Additionally, MD Anderson Cancer Center developed a regimen comprising gemcitabine, busulfan, and melphalan (GBM), noted for its potent synergistic effect in inhibiting lymphoma cell line proliferation 18 .…”

BeEAM Conditioning for Autologous Transplant in Lymphoma: A Review of the Evidence, Safety and Efficacy

“…While the mechanism of action of BCNU-induced IPS has not yet been elucidated, it appears to be dose-dependent [9]. The incidence of IPS associated with BCNU varies widely in the literature, with rates of 1-64% reported [9][10][11][12]. Unsurprisingly, BCNU doses below 450 mg/m 2 appear to be far less problematic [10].…”

Modified BEAC conditioning regimen with idarubicin followed by autologous hematopoietic stem cell transplantation is safe and effective for invasive B-cell non-Hodgkin’s lymphoma patients

“…With the aim of obtaining a higher anti-lymphoma activity and/or reducing the toxic effects, a number of studies suggested the possibility of improving the outcomes of NHL patients through modifing the conditioning regimens [8][9][10]. BuCyE (busulfan, cyclophosphamide, and etoposide) [11,12] and Benda-EAM (bendamustine, etoposide, cytarabine, and melphalan) [13][14] were approved to be effective and safe for NHL patients [15][16].…”