title: Lenalidomide plus melphalan without prednisone for previously untreated older patients with multiple myeloma: a phase II trial.
abstract: BACKGROUND
  We conducted a phase II trial that evaluated the tolerability and efficacy of combining lenalidomide with melphalan in previously untreated patients with multiple myeloma who were not candidates for autologous stem cell transplantation.
  
  
  METHODS
  After a run-in phase of 6 patients, we planned to conduct a randomized phase II selection-design trial that assessed 2 dose levels of lenalidomide, given days 1 to 21, combined with melphalan, given days 1 to 4, and every 28 days. Planned doses of melphalan were 9 mg/m(2)/d and respective doses of lenalidomide were 10 and 20 mg/d (M9L10 and M9L20). Coprimary endpoints were the frequency of dose-limiting Planned doses of melphalan were 9 mg/m(2)/d and respective doses of lenalidomide were 10 and 20 mg/d (M9L10 and M9L20). toxicities (DLT) and complete response (CR).
  
  
  RESULTS
  Four patients received M9L10; all experienced DLTs, which resulted in closure of this cohort. When using the same schedule, we then sequentially tested M6L10 (melphalan 6 mg/m(2) on days 1 to 4 and lenalidomide 10 mg/d on days 1 to 21 every 28 days) (6 patients), M4L15 (melphalan 4 mg/m(2) on days 1 to 4 and lenalidomide 15 mg/d on days 1 to 21 every 28 days) (6 patients), and M5L10 (melphalan 5 mg/m(2) days 1 to 4 and lenalidomide 10 mg/d days 1 to 21 every 28 days) (34 patients). In each cohort, the DLT endpoint was reached because of severe and prolonged hematologic toxicity. At the final dose level, M5L10, 20 of 27 patients experienced DLTs within their first 3 cycles; among 10 patients who received at least 6 cycles, none achieved a CR.
  
  
  CONCLUSIONS
  Combining lenalidomide plus melphalan without prednisone is associated with substantial hematologic toxicity that precludes cyclical administration of adequate drug doses.
authors.affiliation: Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia, Canada. d.white@dal.ca
authors.forename: Darrell J
authors.initials: DJ
authors.lastname: White
authors.forename: Nizar J
authors.initials: NJ
authors.lastname: Bahlis
authors.forename: Deb C
authors.initials: DC
authors.lastname: Marcellus
authors.forename: Andrew
authors.initials: A
authors.lastname: Belch
authors.forename: A Keith
authors.initials: AK
authors.lastname: Stewart
authors.forename: Christine
authors.initials: C
authors.lastname: Chen
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kovacs
authors.forename: David A
authors.initials: DA
authors.lastname: Macdonald
authors.forename: Donna E
authors.initials: DE
authors.lastname: Reece
authors.forename: Tony
authors.initials: T
authors.lastname: Reiman
authors.forename: Erica
authors.initials: E
authors.lastname: Harnett
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Meyer
authors.forename: Judy-Anne W
authors.initials: JA
authors.lastname: Chapman
authors.forename: Stephen
authors.initials: S
authors.lastname: Couban
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D009367:Neoplasm Staging; D011241:Prednisone / Q000008:administration & dosage; D033581:Stem Cell Transplantation / Q000379:methods; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D014182:Transplantation, Autologous
chemical_list: D013792:Thalidomide; D000077269:Lenalidomide; D008558:Melphalan; D011241:Prednisone