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

Hagop M Kantarjian,Richard E Clark,Viviane Dubruille,Richard A Larson,Paola Aimone,Silvia Cacciatore,Dong Wook Kim ,Philipp Le Coutre,M Mędraś ,Ksenia Titorenko,Giuseppe Saglio,Surapol Issaragrisil,Timothy P Hughes,Ian W Flinn,Gabriel Étienne ,Sławomira Kyrcz‐Krzemień ,Carla Boquimpani,Ricardo Pasqüini ,Maria Aparecida Zanichelli ,Israel Bendit,Andreas Hochhaus

doi:10.1038/s41375-020-01111-2

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 MR4.5 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.

Highlights

Nilotinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor (TKI) widely used for the treatment of patients with newly diagnosed Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP) or imatinib-resistant or imatinib-intolerant Ph+ CML in CP orThese authors contributed : Hagop M
The cumulative rates of major molecular response (MMR), MR4, and MR4.5 were higher by 5 years and by 10 years with nilotinib than with imatinib
In the combined analysis of the 2 nilotinib arms, response rates were higher at 5 years and 10 years with nilotinib versus imatinib, and patients in the nilotinib arms reached MMR and MR4.5 in a shorter time than those in the imatinib arm

Summary

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Nilotinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor (TKI) widely used for the treatment of patients with newly diagnosed Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP) or imatinib-resistant or imatinib-intolerant Ph+ CML in CP or. Throughout the first 5 years of follow-up in the pivotal phase 3 ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Newly Diagnosed Patients) study, treatment with nilotinib resulted in higher rates of major molecular response (MMR; BCR-ABL1 ≤ 0.1% on the International Scale [BCR-ABL1IS]) and deep molecular response (DMR; including MR4 [BCR-ABL1IS ≤ 0.01%] and MR4.5 [BCRABL1IS ≤ 0.0032%]) over imatinib as frontline therapy for newly diagnosed CML-CP [4, 5]. With 5 years of follow-up, 54% of patients on nilotinib 300-mg twice-daily and 52% of patients on nilotinib 400-mg twice-daily achieved MR4.5 compared. To allow a comprehensive assessment of the long-term benefits and risks of nilotinib and imatinib in patients with CML-CP, the final results from ENESTnd after ≥10 years of follow-up are reported here

Study design and patients

Results

Discussion

Compliance with ethical standards