Bendamustine Plus Melphalan As Conditioning Regimen for Second Autologous Stem Cell Transplantation in Patients with Multiple Myeloma: Single Centre Experience

Background: Bendamustine has a proved activity in hematological malignancies including both first line and relapsed multiple myeloma (MM). Moreover Bendamustine is generally well tolerated, with the majority of adverse events mainly limited to myelosuppression. Recently Mark et al published a phase I trial adding escalating doses of Bendamustine to the current standard conditioning of Melphalan 200 mg/m² (HDM) in patients with MM at their first transplant. No transplant related mortality (TRM) was observed and the regimen was well tolerated. Recently was stated that double autologous stem cell transplantation (ASCT) improve the outcome of patients achieving a poor response after first ASCT. Although HDM is the standard for conditioning in MM, in some cases the CR rate is lower than expected. In this trial we evaluate feasibility and efficacy of the association of Bendamustine and Melphalan (BM) as conditioning regimen to second ASCT in patients with MM.

Methods: This study was approved by local ethic committee.Between January and June 2014, 12 patients with MM underwent second ASCT following BM as conditioning regimen. The median age was of 56 years (range 40-66), 8 male and 4 female with a diagnosis of MM, stage IIIA (n=7), IIIB (n=4) and IIA (n=1). All patients received a bortezomib-containing regimen as first-line induction therapy and received Melphalan 200 mg/m² as conditioning regimen before the first ASCT. All patients urderwent second ASCT following Bendamustine (100 mg/m² days -4 and -3) and Melphalan (140 mg/m² day -2) as conditioning regimen. G-CSF were given at day 5 after transplant.

Results: A median number of 4.9x10⁶/kg of CD34+ cells (range: 4-6.2) was infused. All patients engrafted, with median time to reach neutrophil>500/µl and platelet >20.000/µl of 12 days (range, 11 to 15) and 14 (range, 11 to 19), respectively. Overall, the BM regimen was well tolerated. Almost all patients experienced mucositis, nausea and diarrhea but all events were of grade 1 or 2 (grade 3 diarrhea occurred in only 1 patient). Four patients (33%) had fever (grade 1 or 2) that was clinically identified in 2 cases (pneumonia and cystitis). The median time of duration of fever was 4 days (range, 2-6). No TRM occurred after at least day + 90 after transplant. Overall, no added toxicity were observed between the first and second ASCT. At day + 90 after first and second transplant response rate was respectively: 1 CR, 10 VGPR, 1 PR and 4 CR, 5 VGPR, 1 PR, 2 too early. Three patients in VGPR after first transplant converted to CR after second ASCT.

Conclusion: Bendamustine plus Melphalan is feasible as conditioning regimen for second ASCT in patients with MM. The regimen was well tolerated and the toxicity profile of ASCT with conditioning regimens BM or Melphalan is comparable. Longer follow-up is needed to evaluate conversion rate and survival.

References: Mark TM et al. A phase 1 study of bendamustine and melphalan conditioning for autologous stem cell transplantation in multiple myeloma. Biol Blood Marrow Transplant. 2013 May;19(5):831-7.