title: Imatinib in very elderly patients with chronic myeloid leukemia in chronic phase: a retrospective study.
abstract: BACKGROUND
  A large number of chronic myeloid leukemia (CML) patients are treated with imatinib mesylate outside of clinical trials, which may not be representative of common clinical practice. The age of CML patients enrolled within controlled clinical studies is lower with respect to patients included in population-based registries.
  
  
  METHODS
  To describe the safety and tolerability of imatinib in very elderly CML patients in chronic phase, 211 chronic-phase CML patients aged >75 years were retrospectively analyzed using data collected from 31 institutions in Italy.
  
  
  RESULTS
  The median age at imatinib start was 78.6 years [interquartile range (IR) 76.3-81.4], median time from diagnosis to imatinib start was 1.2 months (IR 0.5-3.7). The starting dose of imatinib was 400 mg/day in 144 patients (68.2 %), >400 mg/day in 4 patients (2.0 %), and <400 mg/day in 63 patients (29.8 %); overall, 94 patients (44.5 %) needed a dose reduction and 27 (12.7 %) discontinued imatinib for toxicity. Grade 3-4 hematologic and extrahematologic toxicities were observed in 40 (18.9 %) and 45 (21.3 %) patients, respectively. After a median observation of 29.8 months (IR 13.0-55.6), 203/211 patients had at least 6 months of observation on imatinib or discontinued before and were evaluable for response and outcome; of them, 183 patients (90.2 %) achieved a complete hematologic response (CHR). Among these 183 patients in CHR, 14 refused any other karyotypic or molecular evaluation, 24 achieved CHR only, and 145 (71.4 %) achieved a cytogenetic response (CyR) of any grade, which was complete (CCyR) in 129 (63.5 %). Among the 129 patients with CCyR, 95 (46.7 %) achieved a major molecular response (MMolR). By multivariate regression analysis, late chronic phase (p = 0.001) and grade 3-4 extrahematologic toxicity (p = 0.007) maintained a negative independent prognostic impact for CCyR, while late chronic phase (p = 0.026), grade 3-4 extrahematologic toxicity (p = 0.007), and lower initial dose of imatinib (p = 0.044) maintained a negative independent prognostic impact for MMolR. The 2-year and 4-year overall survival were 92.6 % (95 % CI 88.7-96.5) and 78.0 % (95 % CI 71.2-84.8), respectively.
  
  
  CONCLUSIONS
  Results from this large cohort of patients show that no upper age limit should be applied for the administration of imatinib to patients with chronic-phase CML; the very elderly, including those with concomitant severe diseases, should be offered this treatment. The role of a reduced starting dose of imatinib warrants further studies.
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, Università, La Sapienza, Via Benevento 6, 00161, Rome, Italy. rob.lati@libero.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Latagliata
authors.forename: Dario
authors.initials: D
authors.lastname: Ferrero
authors.forename: Alessandra
authors.initials: A
authors.lastname: Iurlo
authors.forename: Francesco
authors.initials: F
authors.lastname: Cavazzini
authors.forename: Fausto
authors.initials: F
authors.lastname: Castagnetti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Abruzzese
authors.forename: Carmen
authors.initials: C
authors.lastname: Fava
authors.forename: Massimo
authors.initials: M
authors.lastname: Breccia
authors.forename: Mario
authors.initials: M
authors.lastname: Annunziata
authors.forename: Fabio
authors.initials: F
authors.lastname: Stagno
authors.forename: Mario
authors.initials: M
authors.lastname: Tiribelli
authors.forename: Gianni
authors.initials: G
authors.lastname: Binotto
authors.forename: Giovanna
authors.initials: G
authors.lastname: Mansueto
authors.forename: Antonella
authors.initials: A
authors.lastname: Gozzini
authors.forename: Sabina
authors.initials: S
authors.lastname: Russo
authors.forename: Laura
authors.initials: L
authors.lastname: Cavalli
authors.forename: Enrico
authors.initials: E
authors.lastname: Montefusco
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gugliotta
authors.forename: Michele
authors.initials: M
authors.lastname: Cedrone
authors.forename: Antonella
authors.initials: A
authors.lastname: Russo Rossi
authors.forename: Paolo
authors.initials: P
authors.lastname: Avanzini
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pregno
authors.forename: Endri
authors.initials: E
authors.lastname: Mauro
authors.forename: Antonio
authors.initials: A
authors.lastname: Spadea
authors.forename: Francesca
authors.initials: F
authors.lastname: Celesti
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Giglio
authors.forename: Alessandro
authors.initials: A
authors.lastname: Isidori
authors.forename: Monica
authors.initials: M
authors.lastname: Crugnola
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Calistri
authors.forename: Federica
authors.initials: F
authors.lastname: Sorà
authors.forename: Stefano
authors.initials: S
authors.lastname: Storti
authors.forename: Ada
authors.initials: A
authors.lastname: D'Addosio
authors.forename: Giovanna
authors.initials: G
authors.lastname: Rege-Cambrin
authors.forename: Luigiana
authors.initials: L
authors.lastname: Luciano
authors.forename: Giuliana
authors.initials: G
authors.lastname: Alimena
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D015897:Comorbidity; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D007558:Italy / Q000453:epidemiology; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D008297:Male; D060787:Neoplasm Grading; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012074:Remission Induction; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate