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Final outcomes of escalated melphalan 280 mg/m with amifostine cytoprotection followed autologous hematopoietic stem cell transplantation for multiple myeloma: high CR and VGPR rates do not translate into improved survival. Bone Marrow Transplant 2018 Jun 15 PMID: 29907806

Pubmed ID

29907806

Abstract

The most common preparative regimen for autologous transplantation (ASCT) in myeloma (MM) consists of melphalan 200 mg/m (MEL 200). Higher doses of melphalan 220-260 mg/m, although relatively well tolerated, have not shown significant improvement in clinical outcomes. Several approaches have been pursued in the past to improve CR rates, including poly-chemotherapy preparative regimens, tandem ASCT, consolidation, and/or maintenance therapy. Since there is a steep dose-response effect for intravenous melphalan, we evaluated an alternative single ASCT strategy using higher-dose melphalan at 280 mg/m (MEL 280) with amifostine as a cytoprotectant as the maximum tolerated dose determined in an earlier phase I dose escalation trial. We report the final long-term outcomes of MM patients who underwent conditioning with MEL 280 with amifostine cytoprotection followed by ASCT. Although the complete response rate was quite high in the era pre-dating the routine use of novel therapies (proteasome inhibitors, immunomodulatory agents) (49%), the progression-free survival was a disappointing 22 months. The implications of this dichotomy between the excellent depth of ASCT response and progression-free survival are discussed.

Author List

Hari P, Reece DE, Randhawa J, Flomenberg N, Howard DS, Badros AZ, Rapoport AP, Meisenberg BR, Filicko-Ohara J, Phillips GL, Vesole DH

Author

Parameswaran Hari MD Chief, Professor in the Medicine department at Medical College of Wisconsin




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