'Real-life' study of imatinib therapy in chronic phase-chronic myeloid leukemia: A novel retrospective observational longitudinal analysis.
OBJECTIVE
Imatinib is a cornerstone of treatment of chronic myeloid leukemia. It remains unclear whether transient treatment discontinuation or dose changes affect outcome and this approach has not yet been approved for use outside clinical trials.


METHODS
We conducted a retrospective single-institution observational study to evaluate factors affecting response in 'real-life' clinical practice in 138 chronic myeloid leukemia patients in chronic phase treated with imatinib. We used a novel longitudinal data analytical model, with a generalized estimating equation model, to study BCR-ABL variation according to continuous standard dose, change in dose or discontinuation; BCR-ABL transcript levels were recorded. Treatment history was subdivided into time periods for which treatment was given at constant dosage (total 483 time periods). Molecular and cytogenetic complete response was observed after 154 (32%) and 358 (74%) time periods, respectively.


RESULTS
After adjusting for length of time period, no association between dose and cytogenetic complete response rate was observed. There was a significantly lower molecular complete response rate after time periods at a high imatinib dosage.


CONCLUSIONS
This statistical approach can identify individual patient variation in longitudinal data collected over time and suggests that changes in dose or discontinuation of therapy could be considered in patients with appropriate biological characteristics.
a Department of Onco-Hematology , Hematology Unit, Fondazione IRCCS Policlinico San Matteo , Pavia , Italy.
Serena
S
Merante
a Department of Onco-Hematology , Hematology Unit, Fondazione IRCCS Policlinico San Matteo , Pavia , Italy.
Virginia
V
Ferretti
a Department of Onco-Hematology , Hematology Unit, Fondazione IRCCS Policlinico San Matteo , Pavia , Italy.|b Department of Molecular Medicine , University of Pavia , Pavia , Italy.
Chiara
C
Elena
a Department of Onco-Hematology , Hematology Unit, Fondazione IRCCS Policlinico San Matteo , Pavia , Italy.
Celeste
C
Calvello
a Department of Onco-Hematology , Hematology Unit, Fondazione IRCCS Policlinico San Matteo , Pavia , Italy.
Barbara
B
Rocca
a Department of Onco-Hematology , Hematology Unit, Fondazione IRCCS Policlinico San Matteo , Pavia , Italy.
Rita
R
Zappatore
a Department of Onco-Hematology , Hematology Unit, Fondazione IRCCS Policlinico San Matteo , Pavia , Italy.
Paola
P
Cavigliano
a Department of Onco-Hematology , Hematology Unit, Fondazione IRCCS Policlinico San Matteo , Pavia , Italy.
Ester
E
Orlandi
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage / Q000627:therapeutic use*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D064887:Observational Studies as Topic; D012189:Retrospective Studies; D055815:Young Adult
D000970:Antineoplastic Agents; D000068877:Imatinib Mesylate
Chronic myeloid leukemia; Imatinib; Novel statistical analysis; ‘Real-life’