Autologous Stem Cell Transplantation with Benda-BEAM (Bendamustine, Etoposide, Cytarabine, Melphalan) in Aggressive Non Hodgkin and Hodgkin´s Lymphoma

Autologous Stem Cell Transplantation (ASCT) is standard of care in relapsed diffuse large B-cell lymphoma (DLBCL) and other lymphoproliferative disorders (relapsed Hodgkin´s disease, mantle or T-cell lymphoma). BCNU, Etoposide, Ara-C, Melphalan (BEAM) is a standard conditioning regimen, but BCNU is associated with interstitial pneumonia (range 2 to 20%) and a increased risk of death compared with busulfan or TBI based regimens. Therefore a less toxic regimen might improve the results in (relapsed) lymphoma patients. Bendamustine showed promising results in B- and T-cell lymphoma and dose escalation is safe and feasible. Here we report promising results with bendamustine replacing BCNU in the BEAM regimen described as Benda-BEAM, recently published in a phase two dose finding study (Visani, Blood 2011).

Thirty-eight patients with Hodgkin´s (HL)(n=9) or Non-Hodgkin (n=29) lymphoma were consecutively treated with Benda-BEAM (bendamustine on two consecutive days at a dose of 200 mg/m²per day). Ten patients were diagnosed with DLBCL, also ten patients with mantle cell lymphoma, four patients with an anaplastic T-cell lymphoma, four patients with follicular lymphoma and one patient with an greyzone lymphoma. Twenty-four patients were male and fourteen female with a median age of 52 years (range 22-71) and 25% were above the age of sixty. The median lines of previous therapies were 2 (range: 1-4). 36 patients were treated with Benda-BEAM and 2 patients with mantle cell lymphoma received additionally Zevalin.

All patients had chemosensitive disease and before transplantation 31 patients (82%) were in complete (CR) and 7 (18%) in partial remission (PR). A median number of 4,10*10⁶ CD34+ cells/kg (range: 1,60-11,10) were infused. All patients showed engraftment with a median time to achieve an absolute neutrophil count > 1*10⁹/L of 10 days (range 7-13) and to platelets >20*10⁹/L of 11 days (range 5-26). The median time of fever was 6 days (range: 0 -22). The most common grade 3 and 4 toxicity during the whole treatment period were diarrhoea (n=10), mucositis (n=7) and febrile neutropenia (n=6), followed by nausea (n=4) and cardiologic toxicities (n=3). There were no pulmonary toxicities observed and no transplant related mortality occurred. After a median follow-up of 22 months, thirty-three patients were evaluable for response, with 21 patients (64%) still in CR, while 12 patients (36%) showed progression after a median time of 6 months after transplantation (range 2-22 months), Until today seven patients (21%) have died (5 DLBCL, 1 HL, 1 mantle cell lymphoma), all due to lymphoma progression. The 1-year PFS is 72% and the 1-year OVS 85%.

Thus Benda-BEAM seems to be feasible with a promising response rate und a randomized phase II trial comparing Benda-BEAM with BEAM is planned.