Novel regimens prior to autologous stem cell transplantation for the management of adults with relapsed/refractory non-Hodgkin lymphoma and Hodgkin lymphoma: alternatives to BEAM conditioning

Abstract

High-dose therapy (HDT) followed by autologous stem cell transplant (ASCT) is the standard treatment for relapsed or refractory non-Hodgkin and Hodgkin lymphoma. Until recently, carmustine, etoposide, cytarabine and melphalan (BEAM) was the most commonly used conditioning regimen in this setting, given its acceptable efficacy and tolerability. Despite reasonable success with BEAM, carmustine is associated with a number of acute and late toxicities. Moreover, recent supply and cost issues for this agent have created an urgent need for alternative conditioning regimens. As such, etoposide and melphalan (VP16/MEL) or busulfan, cyclophosphamide, and etoposide (BuCyE) are currently being used with limited success. A number of novel conditioning regimens that replace carmustine with other agents are under investigation, which may provide effective alternatives to BEAM. In considering novel agents to replace carmustine, bendamustine may provide the best alternative, as demonstrated by the results of a number of phase II, multicenter, controlled studies.

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

“…The authors concluded that hydration should be increased in patients receiving high doses of bendamustine to avoid the possibility of renal toxicity (Garciaz et al , ). We agree with this conclusion and with the recommendations of Isidori et al () that patients receiving high doses of bendamustine should be hyperhydrated with at least 2.5 l/m 2 liquid per day, starting hydration 1 day prior to bendamustine administration to avoid renal toxicities, and that this should be strictly monitored.…”

“…No grade III–IV cardiac or hepatic toxicity was reported. Non‐infectious pneumonia and late pulmonary complications described with the use of carmustine, such as chronic interstitial fibrosis (Bhatia et al , ; Isidori et al , ), were not observed in our study. Regarding haematological toxicity, engraftment data are similar to those previously reported with the BEAM or BEAC (BCNU, etoposide, cytarabine, cyclophosphamide) regimens (Caballero et al , ; Jo et al , ) .…”

“…In these retrospective studies, the BEAM regimen or thiotepa-based regimens achieved a 3-year PFS of around 50% in DLBCL patients. However, the lack of randomized trials and the fact that published studies are of several study populations with differing proportions of histologies makes a comparison very difficult (Isidori et al, 2016). In the present trial, patients in CR with a negative FDG-PET at the time of transplant performed better than patients in metabolic PR, as measured by both PFS and OS.…”

“…In these retrospective studies, the BEAM regimen or thiotepa‐based regimens achieved a 3‐year PFS of around 50% in DLBCL patients. However, the lack of randomized trials and the fact that published studies are of several study populations with differing proportions of histologies makes a comparison very difficult (Isidori et al , ).…”

“…However, carmustine is currently unavailable or of very limited availability in some countries (Garciaz et al, 2016). In addition, it has been associated with late pulmonary complications, non-relapse-related late death and secondary tumours (Bhatia et al, 2005;Afessa et al, 2012;Chen et al, 2015;Isidori et al, 2016). Therefore, the substitution of carmustine by other agents could increase efficacy and reduce toxicities associated with the BEAM regimen.…”