Dose-intensified bendamustine and melphalan (BenMel) conditioning before second autologous transplantation in myeloma patients

Hematol Oncol. 2018 Oct;36(4):671-678. doi: 10.1002/hon.2546. Epub 2018 Sep 11.

Abstract

Consolidation in myeloma patients with high-dose melphalan chemotherapy (Mel HDCT) and autologous transplantation (ASCT) is standard of care since more than 2 decades. However, definite cure remains exceptional despite intensive treatment, and improving effectiveness of HDCT remains an unmet clinical need. Combining intensified bendamustine with melphalan may represent an option. We analyzed safety and efficacy of combining dose-intensified bendamustine (200 mg/m2 on days -4/-3) with high-dose melphalan (100 mg/m2 on days -2/-1) before a second (tandem) ASCT in adverse risk myeloma patients after Mel HDCT/ASCT1. Twelve patients received BenMel conditioning before ASCT2 because of high-risk cytogenetics and/or failure to achieve complete remission (CR) after Mel HDCT/ASCT1. Comparing Mel HDCT/ASCT1 and BenMel HDCT/ASCT2, we observed no differences in hematologic recovery and tolerance. Acute renal injury after BenMel conditioning occurred in 3 (25%) patients, but was reversible in all patients, and there were no treatment related deaths. Complete remission rates were increasing from 42% after Mel/ASCT1 to 75% after BenMel/ASCT2. PFS 1 year after ASCT2 was 67%, and OS was 83%. These data suggest that dose-intensified bendamustine with melphalan conditioning is safe and warrants a prospective randomized comparison to standard melphalan HDCT in myeloma patients.

Keywords: autologous transplantation; bendamustine; conditioning; high-dose chemotherapy; intensified; melphalan; myeloma; remission; response.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD34 / immunology
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bendamustine Hydrochloride / administration & dosage
  • Bendamustine Hydrochloride / adverse effects
  • Female
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Melphalan / administration & dosage
  • Melphalan / adverse effects
  • Middle Aged
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / therapy*
  • Transplantation Conditioning / adverse effects
  • Transplantation Conditioning / methods*
  • Transplantation, Autologous

Substances

  • Antigens, CD34
  • Bendamustine Hydrochloride
  • Melphalan