title: A Phase I Trial of High-Dose Lenalidomide and Melphalan as Conditioning for Autologous Stem Cell Transplantation in Relapsed or Refractory Multiple Myeloma.
abstract: Autologous stem cell transplantation (ASCT) conditioned with high-dose chemotherapy has long been established as the standard of care for eligible patients with newly diagnosed multiple myeloma. Despite recent therapeutic advances, high-dose melphalan (HDM) remains the chemotherapy regimen of choice in this setting. Lenalidomide (LEN) in combination with low-dose dexamethasone is recognized as a standard of care for patients with relapsed or refractory multiple myeloma (RRMM), and there is growing support for the administration of LEN as maintenance therapy post-ASCT. In view of the above, the present phase I clinical trial was designed to evaluate the safety and tolerability of high-dose LEN (HDLEN) in patients with RRMM, and to determine the maximum tolerated dose of HDLEN when added to HDM before ASCT. Despite administering HDLEN at doses of up to 350 mg/day, the maximum tolerated dose could not be determined, owing to an insufficient number of dose-limiting toxicities in the 21 patients enrolled in the trial. Conditioning with HDLEN plus HDM was associated with a favorable tolerability profile. Adverse events following ASCT were as expected with HDM. Median progression-free and overall survival were 10 months and 22 months, respectively, in this population of heavily pretreated patients. Our findings suggest that HDLEN in combination with HDM may offer significant potential as a conditioning regimen before ASCT in patients with RRMM. These preliminary findings are now being evaluated further in an ongoing phase II clinical trial.
authors.affiliation: Department of Medicine, Division of Hematology, University of Colorado School of Medicine, Aurora, Colorado. Electronic address: tomer.mark@ucdenver.edu.
authors.forename: Tomer M
authors.initials: TM
authors.lastname: Mark
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York.
authors.forename: Danielle
authors.initials: D
authors.lastname: Guarneri
authors.affiliation: Department of Medicine, Division of Hematology, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Peter
authors.initials: P
authors.lastname: Forsberg
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York.
authors.forename: Adriana
authors.initials: A
authors.lastname: Rossi
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York.
authors.forename: Roger
authors.initials: R
authors.lastname: Pearse
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York.
authors.forename: Arthur
authors.initials: A
authors.lastname: Perry
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York.
authors.forename: Karen
authors.initials: K
authors.lastname: Pekle
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York.
authors.forename: Linda
authors.initials: L
authors.lastname: Tegnestam
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York.
authors.forename: June
authors.initials: J
authors.lastname: Greenberg
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York.
authors.forename: Tsiporah
authors.initials: T
authors.lastname: Shore
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York.
authors.forename: Usama
authors.initials: U
authors.lastname: Gergis
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Mayer
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York.
authors.forename: Koen
authors.initials: K
authors.lastname: Van Besien
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York.
authors.forename: Scott
authors.initials: S
authors.lastname: Ely
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York.
authors.forename: David
authors.initials: D
authors.lastname: Jayabalan
authors.affiliation: Department of Medicine, Division of Hematology, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sherbenou
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York.
authors.forename: Morton
authors.initials: M
authors.lastname: Coleman
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York.
authors.forename: Ruben
authors.initials: R
authors.lastname: Niesvizky
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D020714:Maximum Tolerated Dose; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000401:mortality / Q000628:therapy*; D016879:Salvage Therapy / Q000379:methods*; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019172:Transplantation Conditioning / Q000379:methods* / Q000401:mortality; D014182:Transplantation, Autologous
chemical_list: D013792:Thalidomide; D000077269:Lenalidomide; D008558:Melphalan
keywords: Autologous stem cell transplantation; Lenalidomide; Melphalan; Relapsed and refractory multiple myeloma