Bendamustine‐based conditioning prior to autologous stem cell transplantation (ASCT): Results of a French multicenter study of 474 patients from LYmphoma Study Association (LYSA) centers

Abstract

Carmustine shortage has led to an increase use of alternative conditioning regimens prior to autologous stem cell transplantation for the treatment of lymphoma, including Bendamustine-based (BeEAM). The aim of this study was to evaluate the safety of the BeEAM regimen in a large cohort of patients. A total of 474 patients with a median age of 56 years were analyzed. The majority of patients had diffuse large B-cell lymphoma (43.5%). Bendamustine was administered at a median dose of 197 mg/m /day (50-250) on days-7 and -6. The observed grade 1-4 toxicities included mucositis (83.5%), gastroenteritis (53%), skin toxicity (34%), colitis (29%), liver toxicity (19%), pneumonitis (5%), and cardiac rhythm disorders (4%). Nonrelapse mortality (NRM) was reported in 3.3% of patients. Acute renal failure (ARF) was reported in 132 cases (27.9%) (G ≥2; 12.3%). Organ toxicities and death were more frequent in patients with post conditioning renal failure. In a multivariate analysis, pretransplant chronic renal failure, bendamustine dose >160 mg/m and age were independent prognostic factors for ARF. Pretransplant chronic renal failure, hyperhydration volume, duration of hyperhydration, and etoposide dose were predictive factors of NRM. A simple, four-point scoring system can stratify patients by levels of risk for ARF and may allow for a reduction in the bendamustine dose to avoid toxicity. Drugs shortage may have dangerous consequences. Prospective, comparative studies are needed to confirm the toxicity/efficacy extents from this conditioning regimen compared to other types of high dose therapy.

Benda‐EAM prior to ASCT and renal toxicity: Much ado about nothing

“…We read with interest the paper by Chantepie et al about Benda-EAM high-dose therapy (HDT) prior to ASCT, 1 that put together reallife experience results by collecting retrospective data within LYSA sites. A high rate of grade I-IV toxicities, mainly related to gastrointestinal or mucosal toxicities, and a 12.3% incidence of stage ≥2 acute renal failure (ARF) was reported.…”

“…4 Noteworthy, also 11% of patients receiving standard BEAM at the same institution 4 were admitted to ICU due to septic shock. Chantepie et al 1 reported a rate of ICU admissions of 10.8%, commenting that it is "acceptable". We respectfully disagree, because ICU admission rate after HDT/ASCT in the modern era is 2% to 4%.…”

“…Fourth, for cardiac toxicities, the French reported an incidence of bendamustine-related atrial fibrillation (AF) grades 1 to 4 between 4.8% and 10%. 1,4 However, dose limiting toxicity for bendamustine was defined to be 280 mg/m 2 /day 5 ; at this dose, patients started to experience cardiac complications, mainly arrhythmia. When we fixed the MTD at 200 mg/m 2 , 5 we carefully decided to keep the Bendamustine dose 25% lower than MTD.…”

Bendamustine‐based conditioning prior to autologous stem cell transplantation is associated with high rate of febrile neutropenia and higher mortality

“…The prevalence of hepatitis C in thalassemia patients is variable depending on local disease prevalence but can be as high as 85.4%. 1 Traditionally, the main impediment to the treatment of HCV infection in transfusiondependent thalassemia has been the risk of ribavirin-associated hemolysis. 2 Although the natural history of HCV infection in these patients is unclear, morbidity and mortality is thought to be increased.…”

“…We have read the article by Chantepie et al 1 Table 1. BEAM and BeEAM groups did not differ regarding age, gender, diagnosis, baseline-estimated creatinine clearance, duration of hospitalization, time to neutrophil or platelet recovery (P > 0.05 for all comparisons) showing that two regimens were comparable in terms of baseline and engraftment characteristics.…”