Bendamustine, Etoposide, Cytarabine and Melphalan (BeEAM) Followed By Autologous Stem Cell Transplantation Produce a 3-Year Progression-Free Survival Of 75% In Heavily Pre-Treated Hodgkin and Non-Hodgkin Lymphoma
Authors: Visani Giuseppe , Stefani Pietro Maria , Capria Saveria , Malerba Lara , Galieni Piero , Gaudio Francesco , Specchia Giorgina , Meloni Giovanna , Gherlinzoni Filippo , Giardini Claudio , Falcioni Sadia , Gonella Roberta , Cuberli Francesca , Gobbi Marco , Sarina Barbara , Santoro Armando , Ferrara Felicetto , Rocchi Marco , Ocio Enrique M. , Caballero Maria Dolores , Picardi Paola , Ricciardi Teresa , Loscocco Federica , Isidori Alessandro 
Published: October 2019

Abstract

Background
We previously demonstrated (Visani et al, Blood 2011) the safety of a new conditioning regimen with bendamustine, etoposide, cytarabine, and melphalan (BeEAM) prior to autologous stem cell transplant (ASCT) in resistant/relapsed lymphoma patients (EUDRACTnumber2008-002736-15). Furthermore, this regimen showed significant anti-lymphoma activity (80% CR). At the time of publication (2011), disease type (NHL versus HL) and disease status at transplant (chemosensitive versus chemoresistant) were the only statistically significant variables influencing PFS (p=0.01; p=0.007). However, median follow-up for surviving patients was short (18 months), therefore, it was not possible to draw final conclusions on the efficacy.

Aims
We evaluated the efficacy of the BeEAM regimen in terms of disease-free (DFS) and overall survival (OS) after a median follow-up of 41 months.

Methods
Forty-three patients (median age 47 years, range 18-70) with resistant/relapsed NHL (28) or Hodgkin lymphoma (HL, 15) were consecutively enrolled in the study. Twenty-one patients had primary refractory disease, whereas 22 had relapsed disease, 5 of whom where in second or subsequent relapse, at the time of enrolment.
The study was designed according to Fleming’s method. The primary objective of the study was to determine the 36-months event free survival rate. We fixed the lowest acceptable rate as 40% and the successful rate as 60%, with a significance level a=0.05 and a power 1-b =0.80. At the time of publication, the median follow-up was 18 months, and therefore it was not possible to establish if we had met the primary end-point of the study.

Results
we updated the follow-up at 41 months after transplant. Thirty-one out of 43 patients are still in CR (72%), as documented by both PET and CT scan. Two patients with HL were refractory and rapidly died, whereas 10/43 patients (23%) relapsed after a median time of 7.5 months (range:3-23) from transplant. Five patients died (3 NHL, 2 HL), whereas 5 patients are still alive after relapse. Median PFS and OS were still not reached.
Conversely, 3-year PFS was 75%, allowing our study to met its primary end-point. Interestingly, disease type (HL versus NHL) at transplant is no longer influencing PFS (p=0.7), and still does not influence OS (p=0.1). On the other hand, disease status at transplant (chemosensitive vs chemoresistant) is still a strong predictor of both PFS and OS (p=0.03 and p=0.009, respectively). At present, one patient developed myelodisplasia after transplant. No other late effects were observed up to now.

Conclusions
The new BeEAM regimen met the primary end-point of the study and confirms its safety, after 41 months of follow-up. Interestingly, NHL and HL were not statistically different in terms of both PFS and OS at 41 months of observation.
These data confirm the high efficacy of this regimen in heavily pretreated non-Hodgkin, as well as Hodgkin lymphoma.

Acknowledgments
supported in part by AIL Pesaro Onlus.

Disclosures:
Ocio: Onyx: Consultancy, Research Funding; Novartis: Consultancy; Array Biopharma: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy; Celgene: Consultancy, Research Funding.