title: Older patients with chronic myeloid leukemia (≥65 years) profit more from higher imatinib doses than younger patients: a subanalysis of the randomized CML-Study IV.
abstract: The impact of imatinib dose on response rates and survival in older patients with chronic myeloid leukemia in chronic phase has not been studied well. We analyzed data from the German CML-Study IV, a randomized five-arm treatment optimization study in newly diagnosed BCR-ABL-positive chronic myeloid leukemia in chronic phase. Patients randomized to imatinib 400 mg/day (IM400) or imatinib 800 mg/day (IM800) and stratified according to age (≥65 years vs. <65 years) were compared regarding dose, response, adverse events, rates of progression, and survival. The full 800 mg dose was given after a 6-week run-in period with imatinib 400 mg/day. The dose could then be reduced according to tolerability. A total of 828 patients were randomized to IM400 or IM800. Seven hundred eighty-four patients were evaluable (IM400, 382; IM800, 402). One hundred ten patients (29 %) on IM400 and 83 (21 %) on IM800 were ≥65 years. The median dose per day was lower for patients ≥65 years on IM800, with the highest median dose in the first year (466 mg/day for patients ≥65 years vs. 630 mg/day for patients <65 years). Older patients on IM800 achieved major molecular remission and deep molecular remission as fast as younger patients, in contrast to standard dose imatinib with which older patients achieved remissions much later than younger patients. Grades 3 and 4 adverse events were similar in both age groups. Five-year relative survival for older patients was comparable to that of younger patients. We suggest that the optimal dose for older patients is higher than 400 mg/day. ClinicalTrials.gov identifier: NCT00055874
authors.forename: Ulrike
authors.initials: U
authors.lastname: Proetel
authors.forename: Nadine
authors.initials: N
authors.lastname: Pletsch
authors.forename: Michael
authors.initials: M
authors.lastname: Lauseker
authors.forename: Martin C
authors.initials: MC
authors.lastname: Müller
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hanfstein
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Krause
authors.forename: Lida
authors.initials: L
authors.lastname: Kalmanti
authors.forename: Annette
authors.initials: A
authors.lastname: Schreiber
authors.forename: Dominik
authors.initials: D
authors.lastname: Heim
authors.forename: Gabriela M
authors.initials: GM
authors.lastname: Baerlocher
authors.forename: Wolf-Karsten
authors.initials: WK
authors.lastname: Hofmann
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lange
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.forename: Martin
authors.initials: M
authors.lastname: Wernli
authors.forename: Stephan
authors.initials: S
authors.lastname: Kremers
authors.forename: Rudolf
authors.initials: R
authors.lastname: Schlag
authors.forename: Lothar
authors.initials: L
authors.lastname: Müller
authors.forename: Mathias
authors.initials: M
authors.lastname: Hänel
authors.forename: Hartmut
authors.initials: H
authors.lastname: Link
authors.forename: Bernd
authors.initials: B
authors.lastname: Hertenstein
authors.forename: Markus
authors.initials: M
authors.lastname: Pfirrman
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.forename: Joerg
authors.initials: J
authors.lastname: Hasford
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Hehlmann
authors.forename: Susanne
authors.initials: S
authors.lastname: Saußele
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate