TY - JOUR
T1 - Early responses predict better outcomes in patients with newly diagnosed chronic myeloid leukemia
T2 - Results with four tyrosine kinase inhibitor modalities
AU - Jain, Preetesh
AU - Kantarjian, Hagop
AU - Nazha, Aziz
AU - O’Brien, Susan
AU - Jabbour, Elias
AU - Romo, Carlos Guillermo
AU - Pierce, Sherry
AU - Cardenas-Turanzas, Marylou
AU - Verstovsek, Srdan
AU - Borthakur, Gautam
AU - Ravandi, Farhad
AU - Quintás-Cardama, Alfonso
AU - Cortes, Jorge
N1 - Publisher Copyright:
© 2013 by The American Society of Hematology.
PY - 2013/6/13
Y1 - 2013/6/13
N2 - Early responses to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML)-chronic phase (CP) are associated with improved outcome. We analyzed the impact of such a response on outcomes among patients treated with 4 TKI modalities as frontline therapy in CML-CP. A total of 483 patients who received 400 or 800 mg imatinib, nilotinib, or dasatinib were analyzed. The median follow-up was 72 mo. Landmark analysis at 3 mo by molecular response showed that the cumulative proportions of 3-y event-free survival (EFS) for 3-mo BCR-ABL levels was 95% for those with £1%, 98% for >1% to 10%, and 61% for those with >10% (P 5 .001). The corresponding values by cytogenetic responses were 97% if Ph1 5 0%, 89% if Ph1 5 1% to 35%, and 81% if Ph1 >35% (P 5 .001). Cytogenetic response at 3 mo significantly discriminated for 3-y overall survival (OS): 98%, 96%, and 92%, respectively (P 5 .01). In multivariate analysis, young patients, high Sokal index, and treatment with imatinib 400 significantly predicted for poor (>35%) cytogenetic response at 3 mo. Early responses are predictive for EFS and failure-free survival and to a lesser extent OS, regardless of the treatment modality, although therapies other than standard-dose imatinib result in higher rates of deep early responses. This trial was registered at www.clinicaltrials.gov as ID01-151 NCT00038649, ID01-015 NCT00048672, DM00-163 NCT00333840, ID02-534 NCT00050531, 2005-0422 NCT00254423, and 2005-0048 NCT00129740.
AB - Early responses to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML)-chronic phase (CP) are associated with improved outcome. We analyzed the impact of such a response on outcomes among patients treated with 4 TKI modalities as frontline therapy in CML-CP. A total of 483 patients who received 400 or 800 mg imatinib, nilotinib, or dasatinib were analyzed. The median follow-up was 72 mo. Landmark analysis at 3 mo by molecular response showed that the cumulative proportions of 3-y event-free survival (EFS) for 3-mo BCR-ABL levels was 95% for those with £1%, 98% for >1% to 10%, and 61% for those with >10% (P 5 .001). The corresponding values by cytogenetic responses were 97% if Ph1 5 0%, 89% if Ph1 5 1% to 35%, and 81% if Ph1 >35% (P 5 .001). Cytogenetic response at 3 mo significantly discriminated for 3-y overall survival (OS): 98%, 96%, and 92%, respectively (P 5 .01). In multivariate analysis, young patients, high Sokal index, and treatment with imatinib 400 significantly predicted for poor (>35%) cytogenetic response at 3 mo. Early responses are predictive for EFS and failure-free survival and to a lesser extent OS, regardless of the treatment modality, although therapies other than standard-dose imatinib result in higher rates of deep early responses. This trial was registered at www.clinicaltrials.gov as ID01-151 NCT00038649, ID01-015 NCT00048672, DM00-163 NCT00333840, ID02-534 NCT00050531, 2005-0422 NCT00254423, and 2005-0048 NCT00129740.
UR - http://www.scopus.com/inward/record.url?scp=84881289808&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84881289808&partnerID=8YFLogxK
U2 - 10.1182/blood-2013-03-490128
DO - 10.1182/blood-2013-03-490128
M3 - Article
C2 - 23620574
AN - SCOPUS:84881289808
SN - 0006-4971
VL - 121
SP - 4867
EP - 4874
JO - Blood
JF - Blood
IS - 24
ER -