EHA 2016: Stopping TKIs in CML and Improving Overall Survival in ALL
By Kathy Boltz, PhD
According to findings from the large European Stop TKI (EURO-SKI) Study, stopping tyrosine kinase inhibitor (TKI) therapy in patients with chronic myeloid leukemia (CML) can be safe. Findings were presented at the recently held 2016 European Hematology Association (EHA) 21st Annual Congress and reported here.
The EURO-SKI trial sought to determine what fraction of patients can be sustained in molecular relapse-free remission after stopping TKI treatment and what clinical and biological factors predict a successful TKI-stop. A total of 750 patients with CML were evaluated for molecular relapse-free survival in this large trial.
Since TKI therapy has high cost and a diminished quality of life over time, patients with CML with durable complete molecular responses often ask if they can safely stop kinase inhibitor treatment without relapse.1
At 6 months after stopping TKI therapy, EURO-SKI found that 62% of the patients still maintained treatment response. Treatment response was defined as major molecular response (MMR).
Duration of TKI therapy and a very good therapy response (ie, MR4) prior to stopping were found to be good predictors of a successful stop. However, the other prognostic indicators of gender, age, and risk score were not linked to likelihood of successful stopping of TKI therapy.
After 12 months after stopping TKI therapy, 56% of the patients maintained molecular relapse-free survival, meaning they did not relapse.
“Stopping TKI therapy in a very large cohort of CML patients appears feasible and safe,” said lead author Johan Richter, MD, PhD, Skåne University Hospital, Lund, Sweden.
Among the 750 patients evaluated for molecular relapse after stopping TKI treatment, 347 events of molecular relapse occurred.
Prognostic modeling for patients who received imatinib found that treatment duration and duration of deep molecular relapse significantly correlated with MMR status at 6 months after stopping TKI. Each additional year of imatinib treatment increased the odds of maintaining MMR by 16%.
“We have identified a cutoff suitable for stopping imatinib therapy, which is around 6 years,” said Richter. At 6 months, molecular relapse-free survival was 65.5% for imatinib treatment of longer than 5.8 years and 42.6% for treatment of 5.8 years or less, based on the minimal p-value approach.
The enrolled patients had a median duration of TKI therapy of 7.6 years (range, 3.0-14.2 years), and a median duration of deep molecular remission before stopping TKI therapy of 4.7 years (range, 1.0-13.3 years).
The majority of patients (n=710) received imatinib first line, while some patients (n=35) received nilotinib, and others (n=14) dasatinib. Because of intolerance, 115 patients had been switched to second-line TKIs, with most receiving either nilotinib or dasatinib.
Molecular relapse-free survival slightly declined over time. At 6 months, the molecular relapse-free survival rate was 62%; at 12 months, 56%; at 24 months, 52%; and at 36 months, 49%. For patients who resumed treatment, the median time to restart was 4.1 months.
Richter noted that some of the patients who withdrew from TKI therapy experienced musculoskeletal pain, which was considered newly emergent and mostly transient; 1.2% (n=9) experienced Grade 3 pain, and 235 patients (30.9%) experienced musculoskeletal symptoms.