Impact of early molecular response to nilotinib (NIL) or imatinib (IM) on the long-term outcomes of newly diagnosed patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP): Landmark analysis of 4-year (y) data from ENESTnd.

Abstract

7054^ Background: ENESTnd demonstrated the superiority of NIL to IM in pts with newly diagnosed CML-CP, such as higher rates of molecular response (MR) and reduced risk of progression to accelerated phase (AP)/blast crisis (BC). This landmark analysis of ENESTnd is based on BCR-ABL transcript levels at 3 mo, with 4 y of follow-up. Methods: Rates of major MR (MMR; BCR-ABLIS ≤ 0.1%), MR4.5 (BCR-ABLIS≤ 0.0032%), progression to AP/BC, overall survival (OS), and progression-free survival (PFS) in pts in the NIL 300 mg twice daily (BID; n = 282) and IM 400 mg once daily (QD; n = 283) arms of ENESTnd were evaluated based on 3-mo BCR-ABL levels (≤ 10% vs > 10%). Results: More pts treated with NIL than IM achieved BCR-ABL ≤ 10% at 3 mo (91% vs 67%; Table). Other factors associated with MR at 3 mo included Sokal risk, spleen size, chromosomal abnormalities, white blood cell count, and median dose intensity (for NIL). On both arms, pts with BCR-ABL ≤ 10% at 3 mo had significantly higher rates of MMR and MR4.5and significantly improved PFS and OS than pts with BCR-ABL > 10% at 3 mo. Of the pts with BCR-ABL > 10% at 3 mo, 2 on NIL (8%) and 14 on IM (16%) progressed to AP/BC on study. Half of these progressions occurred between 3 and 6 mo. Analyses of outcomes based on BCR-ABL levels at 6 mo were similar to findings based on 3-mo data. Conclusions: BCR-ABL levels ≤ 10% at 3 mo were associated with superior outcomes, including higher rates of MR4.5 by 4 y and lower risk of disease progression. More pts treated with NIL than IM achieved this early level of MR. Clinical trial information: NCT00471497. [Table: see text]