Treatment-free remission in chronic myeloid leukemia patients treated front-line with nilotinib: 10-year follow- up of the GIMEMA CML 0307 study

We report the final analysis, with a 10-year follow-up, of the phase II study GIMEMA CML 0307 (NCT 00481052), which enrolled 73 adult patients (median age 51 years; range, 18-83) with newly diagnosed chronic-phase chronic myeloid leukemia to in-vestigate the efficacy and the toxicity of front-line treatment with nilotinib. The initial dose was 400 mg twice daily; the dose was reduced to 300 mg twice daily as soon as this dose was approved and registered. The 10-year overall survival and pro-gression-free survival were 94.5\%. At the last contact, 36 (49.3\%) patients were continuing nilotinib (22 patients at 300 mg twice daily, 14 at lower doses), 18 (24.7\%) patients were in treatment-free remission, 14 (19.2\%) were receiving other tyrosine-kinase inhibitors and four (5.5\%) patients have died. The rates of major and deep molecular responses by 10 years were 96\% and 83\%, respectively. The median times to major and deep molecular response were 6 and 18 months, respectively. After a median duration of nilotinib treatment of 88 months, 24 (32.9\%) patients discontinued nilotinib while in stable deep molecular response. In these patients, the 2-year estimated treatment-free survival was 72.6\%. The overall treatment-free remission rate, calculated on all enrolled patients, was 24.7\% (18/73 patients). Seventeen patients (23.3\%), at a median age of 69 years, had at least one arterial obstructive event. In conclusion, the use of nilotinib front-line in chronic phase chronic myeloid leukemia can induce a stable treatment-free remission in a relevant number of patients, although cardiovascular toxicity re-mains of concern.