Long-term outcome with dasatinib after imatinib failure in chronic-phase chronic myeloid leukemia: follow-up of phase 3 study
Mené sur 670 patients atteints d'une leucémie myéloïde chronique résistante à l'imatinib et en phase chronique, cet essai de phase III analyse les résultats à long terme (6 ans) d'un traitement à l'aide de dasatinib
We present long-term follow-up of a dasatinib phase 3 study of patients with imatinib-resistant/ intolerant chronic myeloid leukemia (CML). In the CA180-034 study, 670 patients with imatinib-resistant/-intolerant CML in chronic phase (CML-CP) received dasatinib 100 mg once daily (100qd), 50 mg twice daily (50bid), 140 mg once daily (140qd), or 70 mg twice daily (70bid). At 6 years, 188/670 patients (28%) remained on study treatment. Estimated 6-year protocol-defined progression-free survival (PFS) rates were 49%/51%/40%/47% (100qd/50bid/140qd/70bid), and estimated 6-year overall survival (OS) rates were 71%/74%/77%/70% (intent-to-treat population, including protocol-defined progression or death after discontinuation). Estimated 6-year rates of survival without transformation on study treatment were 76%/80%/83%/74%. Major molecular response was achieved in 43% (100qd) and 40% (all other arms) of patients by 6 years. Molecular and cytogenetic responses at 3 and 6 months were highly predictive of PFS and OS. Notably, estimated 6-year PFS rates based on ≤1%, >1-10%, and >10% BCR-ABL transcripts at 3 months were 68%, 58%, and 26%, respectively. Most adverse events occurred by 2 years. Imatinib-resistant/-intolerant patients with CML-CP can experience long-term benefit with dasatinib therapy, particularly if achieving BCR-ABL ≤10% at 3 months. This study was registered at ClinicalTrials.gov: NCT00123474.