BEAM or BeEAM High-Dose Chemotherapy Followed By ASCT: A Single Center Comparative Analysis of Toxicity
Authors: Ribrag Vincent , Saleh Khalil , Danu Alina , Koscielny Serge , Pilorge Sylvain , castilla-Lorente Cristina , Ghez David , Lazarovici Julien , Michot Jean-Marie , Lapierre Valerie , Alexandrova Kamelia , Arfi-Rouche Julia , Bourhis Jean-Henri 
Published: October 2019

Abstract
Introduction:
The BEAM (carmustine (BCNU), etoposide, aracytin and melphalan) standard conditioning regimen in autologous stem-cell transplantation is widely used since 1990 in patients with relapsed/refractory non Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL) who remain sensitive to salvage therapy. Recently, a phase Ib-II feasibility study using bendamustine rather than BCNU in the same indication was reported, but was not really compared to BEAM concerning safety. We report herein a safety analysis of Bendamustine-EAM (BeEAM) with a control BEAM counterpart paired cohort (2/1).
Methods:
We performed a case control retrospective study of patients with NHL and HL who underwent high-dose chemotherapy (HDC) with BeEAM regimen between January 2015 and December 2015. We matched each BeEAM patient with two patients having the same age, sex and number of treatment lines who underwent BEAM and ASCT between January 2008 and December 2014. No patient presented significant comorbidity. The BEAM regimen consisted in BCNU on day -6 (300mg/m2) cytarabine daily from day -6 to day -3 (200mg/m2 every 12 hours), etoposide daily from day -6 to day -3 (100mg/m2 every 12 hours) and melphalan on day -2 (140mg/m2). A similar scheme was adopted in BeEAM arm with bendamustine on day -6 and -5 (100mg/m2/d) replacing BCNU. Autologous stem cells were reinfused on day 0. Unfractionated heparin was used with Bendamustine to prevent veno-occlusive disease. Pegfilgrastim 6mg was injected subcutaneously on day 4. Febrile neutropenia was treated according to ESMO guidelines.
Results:
One hundred and two patients (68 BEAM and 34 BeEAM) were analyzed. Median age was 48 years in both arms. 61.8% of patients were male and 38.2% female. A median number of 4.4 x106 CD34 were reinfused in the two groups. The median time to neutrophils recovery (> 0.5 x109) was similar between the two arms (9.06 vs 8.86 days, p=0.3). Grade 3 or greater diarrhea according to Commun Terminology Criteria for Adverse Events (CTCAE v4.03) classification was significantly more frequent in BeEAM patients (44 vs 13.2%, p=0.001). Median time to hospital discharge was significantly longer in BeEAM group (23 vs 20.8 days, p=0.0047). The median loss of weight during hospitalization was significantly greater in BeEAM patients (3.3 vs 1.9 kg, p=0.014). The median number of days with fever >38°C and with intravenous antibiotics was significantly higher in BeEAM group (6.06 vs 3.38, p<0.001; 10.76 vs 8.22, p=0.0012 respectively). Five patients in BeEAM arm (14.7%) and 3 patients in BEAM (4.4%) developed grade 2-3 liver cytolysis. Four patients in BeEAM arm developed grade 1 renal toxicity. Six patients presented bacteremia (17.6%) in BeEAM versus 8 patients (11.7%) in BEAM arm. Incidence of mucositis, nausea and vomiting was similar between the two groups. Four patients in the BeEAM arm were rehospitalized for recurrent fever three to five days after discharge. No death occurred in both groups during the ASCT procedure.
Conclusion:
Our results based on retrospective case-control study suggest that BeEAM conditioning regimen followed by ASCT seems to be more toxic than the standard BEAM regimen.

Disclosures
Ribrag: gilead: Membership on an entity's Board of Directors or advisory committees; infinity: Membership on an entity's Board of Directors or advisory committees; nanostring: Membership on an entity's Board of Directors or advisory committees; pharmamar: Membership on an entity's Board of Directors or advisory committees; nanostring: Membership on an entity's Board of Directors or advisory committees; ESAI: Membership on an entity's Board of Directors or advisory committees; incyte: Membership on an entity's Board of Directors or advisory committees; incyte: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; ESAI: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; servier: Consultancy; argenX: Research Funding. Michot:Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees.