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Final outcomes of escalated melphalan 280 mg/m2 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 2019 Feb;54(2):293-299

Date

06/17/2018

Pubmed ID

29907806

DOI

10.1038/s41409-018-0261-y

Scopus ID

2-s2.0-85048569397 (requires institutional sign-in at Scopus site)   10 Citations

Abstract

The most common preparative regimen for autologous transplantation (ASCT) in myeloma (MM) consists of melphalan 200 mg/m2 (MEL 200). Higher doses of melphalan 220-260 mg/m2, 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/m2 (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 Adjunct Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adult
Aged
Amifostine
Cytoprotection
Disease-Free Survival
Dose-Response Relationship, Drug
Female
Hematopoietic Stem Cell Transplantation
Humans
Male
Maximum Tolerated Dose
Melphalan
Middle Aged
Multiple Myeloma
Prospective Studies
Remission Induction
Transplantation Conditioning
Transplantation, Autologous
Treatment Outcome