Successful Stem Cell Mobilization and Autologous Stem Cell Transplantation after Pretreatment Consisting of Bendamustine, Prednisone and Bortezomib (BPV) in 35 Patients with Newly Diagnosed/Untreated Multiple Myeloma
Authors: Poenisch Wolfram , Ploetze Madlen , Holzvogt Bruno , Andrea Marc , Zehrfeld Thomas , Hammerschmidt Doreen , Schwarz Maik , Edelmann Thomas , Becker Cornelia , Hoffmann Franz-Albert , Schwarzer Andreas , Kreibich Ute , Bourgeois Malvina , Heyn Simone , Jentzsch Madlen , Krahl Rainer , Leiblein Sabine , Schliwa Thomas , Vucinic Vladan , Al-Ali Haifa Kathrin , Behre Gerhard , Lange Thoralf , Niederwieser Dietger 
Published: October 2019

Abstract
Introduction: Bendamustine is a bifunctional alkylating agent with low toxicity that produces both single- and double-strand breaks in DNA, and shows only partial cross resistance with other alkylating drugs. Treatment of patients with newly diagnosed multiple myeloma using Bendamustine and Prednisone in comparison to Melphalan and Prednisone results in superior complete response rate and prolonged time to treatment failure (Poenisch et al, Res Clin Oncol 132: 205-212;2006). So far, however, reliable information on stem cell toxicity and mobilization of stem cells for autologous stem cell transplantation (SCT) after induction treatment with a combination of bendamustine, prednisone and bortezomib (BPV) is missing.
Material and Methods: A retrospective analysis of peripheral blood stem cell mobilization and autologous SCT was performed in 35 patients with multiple myeloma who had received at least two cycles of a BPV induction therapy consisting of bendamustine 60 mg/m2 on days 1 and 2, bortezomib 1.3 mg/m² on days 1, 4, 8 and 11, and prednisone 100 mg on days 1, 2, 4, 8 and 11 between October 2008 and May 2014. The mobilization regimen consisted of cyclophosphamide 4 g/m2 and G-CSF (2x5µg/kg). Apheresis was started as soon as peripheral blood CD34+ counts exceeded 20x106/l with a harvest target of 8x106 CD34+/kg. The minimal accepted target was 2x106 CD34+/kg.
Results: A median number of two (range 1–5) BPV treatment cycles were given to the patients. The majority of the patients (n = 31, 89 %) responded including 2 sCR, 5 nCR, 11 VGPR, and 13 PR. Three patients had MR, and 1 SD. Stem cell mobilization and harvest was successful in all patients. In 19 of 35 patients (54 %) a single apheresis was sufficient to reach the target. The median number of aphereses was one (range 1-4) and the median CD34+ cell-count/kg was 13.5 (range 3.2-33.1) x106. All patients received an autologous SCT. The pre-transplantation conditioning therapy consisted of melphalan 200 mg/m2. In 8 patients with concomitant heart amyloidosis or severe renal insufficiency melphalan dose was reduced to 100 or 140 mg/m2. Engraftment was successful in 34 of 35 patients. The median time to leucocytes count >l×109/l was reached after 11 (range 9–18) days and the time to untransfused platelet count of >50×109/l was 13 (range 10–55) days. 34 patients (97%) responded after the autologous SCT with 11 sCR, 2 CR, 7 nCR, 7 VGPR, and 7 PR. The progression free survival at 18 months was 87 % and overall survival was 92 %.
Conclusion: Stem cell mobilization and autologous SCT is feasible in multiple myeloma patients who have received BPV induction therapy.

Disclosures
Al-Ali: Novartis: Consultancy, Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Lange:Novartis: Consultancy, Honoraria, Research Funding.