Nilotinib versus imatinib in patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): ENESTnd 4-year (y) update.

Abstract

7052^ Background: In the 3-y follow-up (f/u) of ENESTnd, NIL demonstrated superior rates of molecular response and reduced progression to accelerated phase/blast crisis (AP/BC) vs IM. Here, we report results with a minimum f/u of 4 y. Methods: 846 adults with newly diagnosed Philadelphia chromosome–positive CML-CP were randomized to receive NIL 300 mg twice daily (BID; n = 282), NIL 400 mg BID (n = 281), or IM 400 mg once daily (QD; n = 283). Results: NIL continued to demonstrate higher rates of major molecular response (MMR; ≤ 0.1% BCR-ABLIS), MR4 (≤ 0.01%IS), and MR4.5 (≤ 0.0032%IS) vs IM (Table). No new progressions have occurred on treatment on any arm since the 2-y analysis. NIL had significantly lower rates of progression to AP/BC on treatment (n = 2, 3, and 12 on NIL 300 mg BID, 400 mg BID, and IM, respectively) and when including f/u after discontinuation (n = 9, 6, and 19 on NIL 300 mg BID, 400 mg BID, and IM, respectively) and higher overall survival (OS) vs IM. By 4 y, half as many pts acquired new BCR-ABL mutations on study with NIL vs IM (n = 12, 11, and 22 on NIL 300 mg BID, 400 mg BID, and IM, respectively). Since the 3-y analysis, 2 new mutations (1 pt with T315I on NIL 300 mg BID; 1 pt with F317L on IM) were reported. Safety profiles of both drugs were consistent with previous ENESTnd analyses. By 4 y, peripheral arterial occlusive disease (PAOD) events were reported in 4 and 5 pts in the NIL 300 mg BID, and 400 mg BID arms, respectively. No pt in the IM arm had a PAOD event. Conclusions: ENESTnd 4-y data continue to demonstrate the superiority of NIL over IM for achieving deeper responses with lower risk of progression, supporting the use of NIL as frontline therapy in CML-CP. Clinical trial information: NCT00471497. [Table: see text]