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

The ground-breaking PARMA and CORAL trials have substantiated high dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) as standard of care in the treatment of chemosensitive and relapsed Non-Hodgkin’s Lymphoma (NHL) [1,2]. Additionally, the regimen has proven effective in the treatment of relapsed and resistant Hodgkin’s Lymphoma (HL) [3,4]. Globally, carmustine (BCNU), etoposide, cytarabine and melphalan (BEAM) has been the most widely used conditioning regimen of the past 30 years [5]. BEAM conditioning is generally well-tolerated and effective, with the most common toxicity being oral and gastrointestinal mucositis [5]. Despite this, some transplant centres have transitioned from BEAM HDCT to a newer regiment referred to as BeEAM, which replaces BCNU for bendamustine. The movement appears to be primarily driven by a worldwide scarcity of BCNU, which has led to affordability issues. This dramatic rise in drug cost is not insignificant. Between 2013 and 2015, the price of BCNU increased from $200 (CAD) / 100 mg vial to $4,965.14 (CAD) / 100 mg vial. Bendamustine was first synthesized in the former German Democratic Republic in the 1960s [6]. The mechanism of action of bendamustine is unlike that of other alkylating agents and its activity includes apoptosis, inhibition of mitotic checkpoints, and induction of mitotic catastrophe [7]. A phase I-II trial conducted by Visani et al. found bendamustine to be safe and efficacious in the transplant setting, reporting a 100-day transplant-related mortality of 0%. Additionally, 81% of the 77-patient cohort was in complete remission at a median observation of 18 months [6].