Early responses predicts for better outcomes in patients with newly diagnosed CML: results with four TKI modalities
Menée sur 483 patients atteints d'une leucémie myéloïde chronique traitée à l'aide d'imatinib, de nilotinib ou de dasatinib (durée médiane de suivi : 72 mois), cette étude évalue l'association entre une réponse moléculaire précoce et la survie
Early responses to tyrosine kinase inhibitors (TKI) in CML-CP are associated with improved outcome. We analyze the impact of such response on outcomes among patients treated with 4 TKI modalities as frontline therapy in CML-CP. A total of 483 patients who received imatinib 400 mg (n=71), imatinib 800 mg (n=204), nilotinib (n=106) or dasatinib (n=102) were analysed. Median follow-up was 72 months. Landmark analysis at 3-months by molecular response showed that the cumulative proportions of 3-yr EFS for 3-month BCR-ABL levels was 95% for those with ≤1%, 98% for 1-10% and 61% for those with >10%. (p=0.001). Corresponding values by cytogenetic responses were 97% if Ph+ =0%, 89% if Ph+ 1-35%, and 81% if Ph+ >35%. (p=0.001). Cytogenetic response at 3 months significantly discriminated for 3-year OS: 98%, 96%, and 92%, respectively (p=0.01). In multivariate analysis, young patients, high Sokal index and treatment with imatinib 400 significantly predicted for poor (>35%) cytogenetic response at 3 months. Early responses are predictive for EFS and FFS 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. Registered at www.clinicaltrials.gov: ID01-151 NCT00038649, ID01-015 NCT00048672, DM00-163 NCT00333840, ID02-534 NCT00050531, 2005-0422 NCT00254423, 2005-0048 NCT00129740
Blood , résumé, 2013