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

• Published in: Leukemia Vol. 35; no. 2; pp. 440 - 453
• Main Authors: Kantarjian, Hagop M., Hughes, Timothy P., Larson, Richard A., Kim, Dong-Wook, Issaragrisil, Surapol, le Coutre, Philipp, Etienne, Gabriel, Boquimpani, Carla, Pasquini, Ricardo, Clark, Richard E., Dubruille, Viviane, Flinn, Ian W., Kyrcz-Krzemien, Slawomira, Medras, Ewa, Zanichelli, Maria, Bendit, Israel, Cacciatore, Silvia, Titorenko, Ksenia, Aimone, Paola, Saglio, Giuseppe, Hochhaus, Andreas
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2021; Nature Publishing Group
• Subjects: 631/67/1990; 631/67/1990/283/1896; Adverse events; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer Research; Chronic myeloid leukemia; Comparative analysis; Critical Care Medicine; Development and progression; Drug therapy; Evaluation; Female; Follow-Up Studies; Hematology; Humans; Imatinib; Imatinib Mesylate - administration & dosage; Inhibitor drugs; Intensive; Internal Medicine; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - mortality; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Male; Medicine; Medicine & Public Health; Middle Aged; Myeloid leukemia; Nilotinib; Oncology; Prognosis; Pyrimidines - administration & dosage; Remission; Risk assessment; Risk groups; Survival; Survival Rate; Targeted cancer therapy; United States
• ISSN: 0887-6924; 1476-5551; 1476-5551
• DOI: 10.1038/s41375-020-01111-2

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.