Introduction. Nilotinib efficiency as the first line therapy was assessed in randomized company-sponsored and academic trials. However, there is currently limited data on the nilotinib efficacy in patients with chronic myeloid leukemia (CML) beyond clinical trials. We aimed to investigate in a real-life setting the response and the outcome on first-line nilotinib therapy and to evaluate prognostic value of pretreatment time before nilotinib administration in Ukrainian CML patient’s cohort.
Materials and methods. We analysed 64 CML patients followed up in the National Research Center for Radiation Medicine (Kyiv, Ukraine) during the period 2012–2019. All patients were in chronic phase and received nilotinib 600 mg/day. Among examined patients there were 30 (46.9%) men and 34 (53.1%) women. The median age was 45 years (21–82 years). The majority of patients (78%) received prior treatment lasting from 1 to 177 months (Me = 7.5 months). Median of follow-up was 47 months (6-84) months. Molecular monitoring of nilotinib therapy was performed by real-time RT-PCR at 3, 6, and 12 months of therapy and every 6 months thereafter. Cumulative incidence of complete cytogenetic response (CCR), major molecular response (MMR), deep molecular response (MR4) and long-term overall survival (OS), event-free survival (EFS), and progression-free survival (PFS) were evaluated.
Results. The tumor clone reduction to the level of MMR at 12 months of nilotinib therapy (optimal response) was detected in 63.7% of patients. Therapy failure at 12 months was registered in 22.8 % patients. In 13.5% of patients at 12 months of therapy was recorded only CCR. They formed a “warning” group. The MR4 rate at 24 months was 39.2%. In the entire follow-up period, of the 52 patients (81.2%) who had a tumor clone reduction to CCR and beyond, none lost achieved molecular or cytogenetic response. Two patients progressed to accelerated phase followed with blastic crisis. Five-year EFS, PFS and OS rates for all patients were 96.3%, 96.3% and 94.2%, respectively. We revealed significant reduction in the incidence of MMR (p = 0.028) at 12 months and an increase in the primary resistance rate (p = 0.003) in patients with a pretreatment period of more than 12 months compared with patients receiving prior therapy for less than 12 months.
There was a positive correlation between the duration of treatment before nilotinib administration and the development of primary resistance after 12 months of nilotinib therapy (Spearman correlation coefficient ρ = 0.434, p = 0.001), as well as a negative correlation between the duration of treatment before nilotinib administration and optimal response at 12 months of nilotinib therapy (Spearman correlation coefficient ρ = –0.385, p = 0.003). Kaplan-Meier analysis showed significant reduction in the rate of CCR, MMR and MR4 in patients with duration of nilotinib treatment more 12 months. No statistically significant differences were found in the 5-year PFS and OS rates in patients with different pretreatment term.
Conclusion: The use of nilotinib in patients with chronic phase CML is extremely effective. Timely nilotinib administration as the first line of TKI therapy significantly reduces the risk of primary resistance development.
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