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

Abstract

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 (CP)-chronic myeloid leukemia (CML) to investigate the efficacy and the toxicity of front-line treatment with nilotinib (NIL). 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 progression-free survival were 94.5%. At the last contact, 36 (49.3%) patients were continuing NIL (22 patients at 300 mg twice daily, 14 at lower doses), 18 (24.7%) patients were in treatment-free remission (TFR), 14 (19.2%) were receiving other tyrosinekinase inhibitors and 4 (5.5%) patients have died.

The rates of major (MMR) and deep (MR4) molecular responses by 10 years were 96% and 83%, respectively. The median time to MMR and MR4 were 6 and 18 months, respectively. After a median duration of NIL treatment of 88 months, 24 (32.9%) patients discontinued NIL while in stable deep molecular response. In these patients, the 2-years estimated treatment-free survival was 72.6%. The overall TFR 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 NIL front-line in CP-CML can induce a stable TFR in a relevant number of patients, although cardiovascular toxicity remains of concern