Long term follow-up of nilotinib in treatment of patients with chronic myeloid leukemia intolerant or refractory to imatinib
For more than two decades, tyrosine kinase inhibitors (TKIs) represent the revolution of treatment for patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML). Imatinib, the first-generation TKI, is a well-established first-line treatment whose efficacy resulted in substantially prolonged overall survival, bringing life expectancy closer to that of the general population. Nilotinib, the second generation TKI, have demonstrated efficacy as the second-line treatment in patients who are intolerant or refractory to imatinib, as well as an alternative first-line option. Despite robust evidence from clinical trials, there are limited real‑world data demonstrating the long term efficacy and safety of nilotinib in these patients. Here, we report a single-center experience with nilotinib in a real-world setting. To the best of our knowledge, this study provides the longest real-world follow-up of nilotinib reported to date.
Materials and Methods/Case Presentation/Objective:
Data on all CML patients treated with nilotinib in the second-line treatment were collected by retrospective chart review from the Division of Hematology, University Hospital of Split, Croatia.
Results/Description/Main Outcome Measure(s): A total of 34 patients (18 females) were included in the study, with a median age of 54 years at the time of diagnosis. Majority of patients were stratified in low or intermediate Sokal risk group with only 18% high risk patients. As the first-line treatment, imatinib was administered to all patients, of whom 24% achieved a major molecular response (MMR). Nilotinib was introduced as the second-line treatment most commonly due to imatinib intolerance (58.8% of patients). A total of 33 (97%) patients achieved or maintained a MMR on nilotinib, of whom 31 (93 %) with a deep molecular response (MR4,5 or more). The median time since diagnosis to MMR was 14 months (range 9 - 19 months). After a median follow-up time of 115 months, median overall survival was not reached with a 10-year overall survival rate of 85%. The most common non-hematologic adverse events (AEs) were pruritic rash, nausea, transient elevation of liver enzymes and peripheral edema. Cardiovascular AEs related to nilotinib were observed in 11 patients (32.4%), with peripheral arterial atherosclerosis being the most common. Of these 11 patients, 10 had at least one pre-existing cardiovascular risk factor.
Conclusion(s).:
A Long-term follow-up in real-world clinical practice has shown that nilotinib is highly effective as the second-line treatment of CML with an acceptable safety profile. However, cardiovascular adverse events occur frequently, and intensive monitoring of cardiovascular risk is required, particularly in patients receiving long-term treatment.
Trademarked Items:
References:
