Switching patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) with residual disease on long-term imatinib (IM) to nilotinib (NIL): ENESTcmr 24-mo follow-up.

Abstract

7053^ Background: The 12-mo results of ENESTcmr demonstrated that switching pts on IM with sustained BCR-ABL positivity to NIL leads to faster, deeper molecular responses (MRs)vs remaining on IM. These deeper molecular responses (MR4.5 [BCR-ABL ≤ 0.0032%IS] or greater) are a prerequisite to enter most treatment-free remission studies. Here, we report 24-mo f/u of ENESTcmr. Methods: Philadelphia chromosome–positive CML-CP pts (N = 207) who achieved a complete cytogenetic response, but had detectable BCR-ABL transcripts after ≥ 2 y on IM, were randomized to receive NIL 400 mg twice daily (BID; n = 104) or continue their IM dose (400/600 mg once daily [QD]; n = 103). Results: By 24 mo, significantly more pts achieved confirmed undetectable BCR-ABL (by RQ-PCR with ≥ 4.5 log sensitivity in 2 consecutive samples) with a switch to NIL vs continuing IM (22.1% vs 8.7%; P = .0087). The increase in the rate of undetectable BCR-ABL from mo 12 to 24 was higher for pts on NIL vs IM (9.6 vs 2.9 percentage points). In pts without MR4.5 at baseline (BL), MR4.5 was achieved by 24 mo in 42.9% vs 20.8% of pts (NIL vs IM; P = .0006). In pts without major molecular response (MMR; ≤ 0.1%IS) at BL, MR4.5 was achieved by 24 mo in 29.2% vs 3.6% of pts (P = .016). No progressions to accelerated phase/blast crisis or deaths occurred on study since the 12-mo f/u. Event-free survival at 24 mo was 96.6% vs 92.8% in the NIL and IM arms, respectively. Discontinuations due to adverse events occurred in 11.5% and 2.9% of pts in the NIL and IM arms. The NIL safety profile was consistent with prior switch studies. Conclusions: By 24 mo, significantly more pts achieved deeper responses (MR4.5and undetectable BCR-ABL) with switch to NIL vs remaining on IM, and the difference between arms in these endpoints increased between 12 and 24 mo. Clinical trial information: NCT00760877. [Table: see text]