Long-term outcomes with frontline nilotinib versus imatinib in newly diagnosed chronic myeloid leukemia in chronic phase: ENESTnd 10-year analysis

Abstract

In the ENESTnd study, with ≥10 years follow-up in patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase, nilotinib demonstrated higher cumulative molecular response rates, lower rates of disease progression and CML-related death, and increased eligibility for treatment-free remission (TFR). Cumulative 10-year rates of MMR and MR^4.5 were higher with nilotinib (300 mg twice daily [BID], 77.7% and 61.0%, respectively; 400 mg BID, 79.7% and 61.2%, respectively) than with imatinib (400 mg once daily [QD], 62.5% and 39.2%, respectively). Cumulative rates of TFR eligibility at 10 years were higher with nilotinib (300 mg BID, 48.6%; 400 mg BID, 47.3%) vs imatinib (29.7%). Estimated 10-year overall survival rates in nilotinib and imatinib arms were 87.6%, 90.3%, and 88.3%, respectively. Overall frequency of adverse events was similar with nilotinib and imatinib. By 10 years, higher cumulative rates of cardiovascular events were reported with nilotinib (300 mg BID, 16.5%; 400 mg BID, 23.5%) vs imatinib (3.6%), including in Framingham low-risk patients. Overall efficacy and safety results support the use of nilotinib 300 mg BID as frontline therapy for optimal long-term outcomes, especially in patients aiming for TFR. The benefit-risk profile in context of individual treatment goals should be carefully assessed.

Fig. 1. Change in molecular response from 5 years to 10 years by molecular response at 5 years in patients with evaluable RQ-PCR at 5 years.

A Nilotinib 300 mg twice daily. B Nilotinib 400 mg twice daily. C Imatinib 400 mg twice daily. ^*Of patients without MMR at 5 years, 33.3% (2/6) achieved MMR or better at 10 years. Of patients without MR⁴ at 5 years, 43.8% (21/48) achieved MR⁴ or better at 10 years. Of patients without MR^4.5 at 5 years, 38.0% (35/92) achieved MR^4.5 at 10 years. ^†All 3 patients were in MR^4.5 at 5 years but died before 10 years (1 due to cardiac arrest, 1 due to multiple organ dysfunction syndrome, and 1 due to pneumonia) while still in MR^4.5. ^‡Both patients were in MR^4.5 at 5 years but were not in MMR before entering the extension phase. ^§Of patients without MMR at 5 years, 43.8% (7/16) achieved MMR or better at 10 years. Of patients without MR⁴ at 5 years, 37.9% (25/66) achieved MR⁴ or better at 10 years. Of patients without MR^4.5 at 5 years, 28.6% (30/105) achieved MR^4.5 at 10 years. ^||One patient was in MR^4.5 at 5 years and in MR⁴ before death due to myocardial infarction. The other patient was in MR⁴ at 5 years and before death due to an unknown reason. ^¶Of patients without MMR at 5 years, 50% (7/14) achieved MMR or better at 10 years. Of patients without MR⁴ at 5 years, 33.8% (22/65) achieved MR⁴ or better at 10 years. Of patients without MR^4.5 at 5 years, 22.7% (22/97) achieved MR^4.5 at 10 years. ^#Both patients were at MMR at 5 years but died before 10 years (1 due to cardiac arrest and 1 due to pneumonia), while still in MMR. ^**Two patients achieved MR^4.5, 1 achieved MR⁴, 2 achieved MMR, and 1 had responses less than MMR in the extension phase.

Fig. 2. Cumulative molecular response rates.

Cumulative proportion of patients with (A) major molecular response (MMR; BCR-ABL1^IS ≤ 0.1%), (B) MR⁴ (BCR-ABL1^IS ≤ 0.01%), and (C) MR^4.5 (BCR-ABL1^IS ≤ 0.0032%). Cumulative MMR, MR⁴, and MR^4.5 results are an analysis of data from the core phase.

Fig. 3. Cumulative rate of TFR eligibility.

Patients were considered eligible for TFR if they achieved MR^4.5 or better in any RQ-PCR assessment after ≥2 years and then maintained sustained DMR for ≥1 year, during which time no RQ-PCR assessment showed a response level worse than MR⁴, a maximum of 2 assessments occurred between MR⁴ and MR^4.5, and the last assessment showed MR^4.5 or better.