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 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.

Target spectrum of the BCR-ABL tyrosine kinase inhibitors in chronic myeloid leukemia

“…It can overcome some imatinib-resistant ABL1 domain-mutated CML cells [13]. Its major molecular response (MMR) and deep molecular response (DMR, defined as 4.0 log reduction of BCR-ABL1 transcript (MR 4.0 ) or deeper) rate in TKInaïve patients with CML CP are 77 and 66% in 5 years, and 82.6% and 73% in 10 years, respectively [6,36].…”

“…In long-term follow-up data, nilotinib-associated CVE risk has been shown to gradually increase over 5 -10 years [36].…”

Current research progress in targeted anti‐angiogenesis therapy for osteosarcoma

“…Compared with traditional treatment methods, targeted therapy is a type of high selectivity and low toxicity cancer treatment that uses drugs or other substances to precisely identify and attack certain types of molecules that are involved in the growth and progression of cancer (eg proteins, nucleic acid fragments and gene products) 4 . Therefore,targeted therapies are currently the focus of much anti‐cancer drug research and have been successfully applied to the treatment of chronic myeloid leukaemia, bowel, lung, breast and renal cancers 5‐8 …”

Current status and novel strategy of CML

“…There was no significant difference in survival among patients treated with nilotinib and imatinib: 10-year PFS/OS rates 86%/88%, 90%/90%, and 87%/88%, with nilotinib 300 mg twice daily, nilotinib 400 mg twice daily, and imatinib 400 mg daily, respectively. Cardiovascular events were more frequently observed in patients treated with nilotinib: 25, 33, and 6% at 10 years with nilotinib 300 mg twice daily, nilotinib 400 mg twice daily, and imatinib 400 mg daily, respectively [40,41]. Other notable side effects include exacerbation of diabetes, fluid retention, pancreatitis, hepatotoxicity, and QT prolongation.…”