Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML)

In the face of competing first-line treatment options for CML, early prediction of prognosis on imatinib is desirable to assure favorable survival or otherwise consider the use of a second-generation tyrosine kinase inhibitor (TKI). A total of 1303 newly diagnosed imatinib-treated patients (pts) were investigated to correlate molecular and cytogenetic response at 3 and 6 months with progression-free and overall survival (PFS, OS). The persistence of BCR-ABL transcript levels > 10% according to the international scale (BCR-ABL IS) at 3 months separated a high-risk group (28% of pts; 5-year OS: 87%) from a group with 1-10% BCR-ABL IS (41% of pts; 5-year OS: 94%; P0.012) and from a group with 1% BCR-ABL IS (31% of pts; 5-year OS: 97%; P0.004). Cytogenetics identified high-risk pts by 35% Philadelphia chromosome-positive metaphases (Ph, 27% of pts; 5-year OS: 87%) compared with 35% Ph (73% of pts; 5-year OS: 95%; P0.036). At 6 months, 1% BCR-ABL IS (37% of pts; 5-year OS: 89%) was associated with inferior survival compared with 1% (63% of pts; 5-year OS: 97%; P0.001) and correspondingly 0% Ph (34% of pts; 5-year OS: 91%) compared with 0% Ph (66% of pts; 5-year OS: 97%; P0.015). Treatment optimization is recommended for pts missing these landmarks.