Bendamustine as part of conditioning of autologous stem cell transplantation in patients with aggressive lymphoma: a phase 2 study from the GELTAMO group

Abstract

Summary We conducted a phase 2 trial to evaluate the safety and efficacy of bendamustine instead of BCNU (carmustine) in the BEAM (BCNU, etoposide, cytarabine and melphalan) regimen (BendaEAM) as conditioning for autologous stem‐cell transplantation (ASCT) in patients with aggressive lymphomas. The primary endpoint was 3‐year progression‐free survival (PFS). Sixty patients (median age 55 [28–71] years) were included. All patients (except one who died early) engrafted after a median of 11 (9–72) and 14 (4–53) days to achieve neutrophil and platelet counts of >0.5 × 109/l and >20 × 109/l, respectively. Non‐relapse mortality at 100 days and 1 year were 3.3% and 6.7%, respectively. With a median follow‐up of 67 (40–77) months, the estimated 3‐year PFS and overall survival (OS) were 58% and 75%, respectively. Patients in partial response at study entry had significantly worse PFS and OS than patients who underwent ASCT in complete metabolic remission, and this was the only prognostic factor associated with both PFS (Relative risk [RR], 0.27 [95% confidence interval {CI} [0.12–0.56]) and OS (RR, 0.40 [95% CI 0.17–0.97]) in the multivariate analysis. BendaEAM conditioning is therefore a feasible and effective regimen in patients with aggressive lymphomas. However, patients not in complete metabolic remission at the time of transplant had poorer survival and so should be considered for alternative treatment strategies.

Bendamustine-EAM versus BEAM regimen in patients with mantle cell lymphoma undergoing autologous stem cell transplantation in the frontline setting: a multicenter retrospective study from Lymphoma Study Association (LYSA) centers

“…This result may be explained by the availability of several second-line therapies, such as ibrutinib, lenalidomide or bortezomib, which considerably improve the duration of survival in MCL patients. 24 Although the feasibility of BeEAM is clearly accepted, 16,17,25 its toxicity profile was not, as almost all conditioning regimens, prospectively compared to other conditioning regimen. We recently reported a large retrospective study on the toxicity of this regimen and we did not found an increased transplant related mortality which remained around 3%.…”

Combining BeEAM with Brentuximab Vedotin for High-Dose Therapy in CD30 Positive Lymphomas before Autologous Transplantation—A Phase I Study

“…In T-cell lymphomas, ASCT in first remission is the preferred consolidation option to improve outcomes, with one study reporting 5-y PFS of up to 49% in AITL [2]. One option as a conditioning regimen before ASCT for these entities is the BeEAM regimen (bendamustine, etoposide, cytarabine, and melphalan) as it offers comparable efficacy to the BEAM (BCNU, etoposide, cytarabine, and melphalan) regimen, avoids BCNU-related pulmonary toxicities, and its commercial availability is decisively more reliable [3][4][5][6][7][8]. However, various other drug combinations have been or are being evaluated [9,10].…”

BeEAM (bendamustine, etoposide, cytarabine, melphalan) prior to autologous stem cell transplant for chemosensitive relapses in patients with follicular lymphoma: a prospective multicentre phase II study in Lymphoma Study Association centres†

“…The BeEAM regimen, through its global safety profile and the reduced recruitment rate consecutive to iDSMB recommendation, led to prematurely stop the trial. The only prospective trial evaluating this conditioning regimen in aggressive lymphoma 5 reported a high toxicity rate with 39 SAEs in 60 (65%) patients including two toxicity‐related mortalities. Infectious SAEs were observed in 18 (30%) patients.…”