Predictive parameters for imatinib failure in patients with chronic myeloid leukemia.
OBJECTIVE
Until recently, imatinib was the standard first-line treatment in chronic myeloid leukemia (CML). The inclusion of nilotinib and dasatinib as first-line options in CML raised a debate on treatment selection. The aim of our study was to analyze predictive parameters for imatinib response as the first-line treatment of CML patients.


METHODS
The study included 168 consecutive patients with chronic phase Philadelphia-positive CML who were diagnosed and treated with Imatinib 400 mg once daily at a single university hospital. Numerous parameters were analyzed in terms of imatinib response including comorbidities as well as occurrence of second malignancies.


RESULTS
After the median follow-up of 87 months in 61 patients (36.3%), the imatinib failure was verified. Cox regression analysis identified hepatomegaly (p = 0.001), leukocytosis ≥ 100 × 109/l (p = 0.001), blood blasts ≥ 1% (p = 0.002), and the presence of additional cytogenetic aberrations (p = 0.002) as predictors of Imatinib failure. Based on these findings, a new prognostic model was developed according to which imatinib failure had 17% (8/47) of patients in low risk, 34.9% (30/86) of patients in intermediate risk, and 76.7% (23/30) of patients in high-risk group (HR = 3.973, 95% CI for HR 2.237-7.053, p < 0.001).


CONCLUSIONS
The new score allows better selection of patients who are suitable for treatment with imatinib and may guideline the clinical decision for front-line treatment of CML.
a Clinic for Hematology , Clinical Center of Serbia , Belgrade , Serbia.|b Medical Faculty , University of Belgrade , Belgrade , Serbia.
Danijela
http://orcid.org/0000-0002-6194-8298
D
Lekovic
a Clinic for Hematology , Clinical Center of Serbia , Belgrade , Serbia.|b Medical Faculty , University of Belgrade , Belgrade , Serbia.
Mirjana
http://orcid.org/0000-0002-8590-0328
M
Gotic
b Medical Faculty , University of Belgrade , Belgrade , Serbia.|c Institute for Medical Statistics , University of Belgrade , Belgrade , Serbia.
Natasa
N
Milic
a Clinic for Hematology , Clinical Center of Serbia , Belgrade , Serbia.
Biljana
B
Zivojinovic
a Clinic for Hematology , Clinical Center of Serbia , Belgrade , Serbia.
Jelica
J
Jovanovic
a Clinic for Hematology , Clinical Center of Serbia , Belgrade , Serbia.|b Medical Faculty , University of Belgrade , Belgrade , Serbia.
Natasa
N
Colovic
a Clinic for Hematology , Clinical Center of Serbia , Belgrade , Serbia.
Violeta
V
Milosevic
a Clinic for Hematology , Clinical Center of Serbia , Belgrade , Serbia.|b Medical Faculty , University of Belgrade , Belgrade , Serbia.
Andrija
A
Bogdanovic
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015415:Biomarkers; D001706:Biopsy; D015897:Comorbidity; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
D000970:Antineoplastic Agents; D015415:Biomarkers; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate
Myeloproliferative neoplasms; chronic myeloid leukemia; imatinib; prediction