title: Melphalan, prednisone, and lenalidomide treatment for newly diagnosed myeloma: a report from the GIMEMA--Italian Multiple Myeloma Network.
abstract: OBJECTIVE
  Lenalidomide has shown significant antimyeloma activity in clinical studies. Oral melphalan, prednisone, and thalidomide have been regarded as the standard of care in elderly multiple myeloma patients. We assessed dosing, efficacy, and safety of melphalan, prednisone, and lenalidomide (MPR) in newly diagnosed elderly myeloma patients.
  
  
  METHODS
  Oral melphalan was administered in doses ranging from 0.18 to 0.25 mg/kg on days 1 to 4, prednisone at a 2-mg/kg dose on days 1 to 4, and lenalidomide at doses ranging from 5 to 10 mg on days 1 to 21, every 28 days for nine cycles, followed by maintenance therapy with lenalidomide alone. Aspirin was given as a prophylaxis for thrombosis.
  
  
  RESULTS
  Fifty-four patients were enrolled and evaluated after completing the assigned treatment schedule. The maximum tolerated dose was defined as 0.18 mg/kg melphalan and 10 mg lenalidomide. With these doses, 81% of patients achieved at least a partial response, 47.6% achieved a very good partial response, and 23.8% achieved a complete immunofixation-negative response. In all patients, 1-year event-free and overall survival rates were 92% and 100%, respectively. At the maximum tolerated dose, grade 3 adverse events included neutropenia (38.1%), thrombocytopenia (14.2%), febrile neutropenia (9.5%), vasculitis (9.5%), and thromboembolism (4.8%); grade 4 adverse events were neutropenia (14.2%) and thrombocytopenia (9.5%).
  
  
  CONCLUSIONS
  Oral MPR therapy is a promising first-line treatment for elderly myeloma patients. Hematologic adverse events were frequent but manageable. A low incidence of nonhematologic adverse events was noted. Aspirin appears to provide adequate antithrombosis prophylaxis.
authors.affiliation: Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliera S. Giovanni Battista, Torino, Italy. appalumbo@yahoo.com
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
authors.forename: Patrizia
authors.initials: P
authors.lastname: Falco
authors.forename: Paolo
authors.initials: P
authors.lastname: Corradini
authors.forename: Antonietta
authors.initials: A
authors.lastname: Falcone
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Raimondo
authors.forename: Nicola
authors.initials: N
authors.lastname: Giuliani
authors.forename: Claudia
authors.initials: C
authors.lastname: Crippa
authors.forename: Giovannino
authors.initials: G
authors.lastname: Ciccone
authors.forename: Paola
authors.initials: P
authors.lastname: Omedè
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Ambrosini
authors.forename: Francesca
authors.initials: F
authors.lastname: Gay
authors.forename: Sara
authors.initials: S
authors.lastname: Bringhen
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
authors.forename: Robert
authors.initials: R
authors.lastname: Knight
authors.forename: Jerome B
authors.initials: JB
authors.lastname: Zeldis
authors.forename: Mario
authors.initials: M
authors.lastname: Boccadoro
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Petrucci
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D020714:Maximum Tolerated Dose; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology