title: Safety of thalidomide in newly diagnosed elderly myeloma patients: a meta-analysis of data from individual patients in six randomized trials.
abstract: Treatment with melphalan-prednisone-thalidomide improves the outcome of patients with multiple myeloma and is now considered a standard of care for patients not eligible for transplantation. However, this treatment is a major source of morbidity. A meta-analysis of data from individual patients (n=1680) in six randomized trials was performed, comparing the effects of melphalan-prednisone-thalidomide versus melphalan-prednisone. The main objective was to estimate the risk of serious adverse events and their impact on outcome. The primary endpoints were the 2-year cumulative incidence of grade 3-4 hematologic and non-hematologic toxicities. At least 75% of the grade 3-4 toxicities occurred during the first 6 months of treatment in both treatment groups. The cumulative incidence of grade 3-4 hematologic toxicities was higher in the melphalan-prednisone-thalidomide group than in the melphalan-prednisone group (28% versus 22%; HR 1.32, 95% CI 1.05-1.66) as was the cumulative incidence of non-hematologic toxicities (39% versus 17%, HR 2.78, 95% CI 2.21-3.50). Grade 3-4 non-hematologic toxicities were significantly increased in patients with poor Performance Status. Occurrence of grade 3-4 non-hematologic toxicities had a negative impact on both progression-free survival (HR 1.24, 95% CI 1.07-1.45) and overall survival, (HR 1.23, 95% CI 1.03-1.47). Besides toxicities, progression-free and overall survival were also negatively affected by advanced International Staging System stage, high creatinine levels and poor Performance Status. Age had a negative impact on survival as well. Although melphalan-prednisone-thalidomide improved outcome, it increased toxicities, especially non-hematologic ones. Serious non-hematologic toxicities, older age, poor Performance Status, and high creatinine levels negatively affected survival.
authors.affiliation: Myeloma Unit, Division of Hematology, University of Turin, AOU S. Giovanni Battista, Torino, Italy. appalumbo@yahoo.com
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
authors.forename: Anders
authors.initials: A
authors.lastname: Waage
authors.forename: Cyrille
authors.initials: C
authors.lastname: Hulin
authors.forename: Meral
authors.initials: M
authors.lastname: Beksac
authors.forename: Sonja
authors.initials: S
authors.lastname: Zweegman
authors.forename: Francesca
authors.initials: F
authors.lastname: Gay
authors.forename: Peter
authors.initials: P
authors.lastname: Gimsing
authors.forename: Xavier
authors.initials: X
authors.lastname: Leleu
authors.forename: Pierre
authors.initials: P
authors.lastname: Wijermans
authors.forename: Gülsan
authors.initials: G
authors.lastname: Sucak
authors.forename: Sara
authors.initials: S
authors.lastname: Pezzatti
authors.forename: Gunnar
authors.initials: G
authors.lastname: Juliusson
authors.forename: Brigitte
authors.initials: B
authors.lastname: Pégourié
authors.forename: Martijn
authors.initials: M
authors.lastname: Schaafsma
authors.forename: Monica
authors.initials: M
authors.lastname: Galli
authors.forename: Ingemar
authors.initials: I
authors.lastname: Turesson
authors.forename: Brigitte
authors.initials: B
authors.lastname: Kolb
authors.forename: Bronno
authors.initials: B
authors.lastname: van der Holt
authors.forename: Ileana
authors.initials: I
authors.lastname: Baldi
authors.forename: Jürgen
authors.initials: J
authors.lastname: Rolke
authors.forename: Giovannino
authors.initials: G
authors.lastname: Ciccone
authors.forename: Marc
authors.initials: M
authors.lastname: Wetterwald
authors.forename: Henk
authors.initials: H
authors.lastname: Lokhorst
authors.forename: Mario
authors.initials: M
authors.lastname: Boccadoro
authors.forename: Philippe
authors.initials: P
authors.lastname: Rodon
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced / Q000175:diagnosis; D006801:Humans; D008297:Male; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate / Q000639:trends; D013792:Thalidomide / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D013792:Thalidomide