Observation in a treatment-free remission in chronic myeloid leukemia patients with a stable deep molecular response in the Russian portion of the international multicenter population based study EUTOS PBS

Introduction. Given the possibility of preserving molecular remission in 40–60 % of patients with chronic myeloid leukemia (CML) with a stable deep molecular response (MR) after discontinuation of tyrosine kinase inhibitors (TKI), it is important to determine the number of candidates for observation in a treatment-free remission (TFR) and terms of treatment cancellation. Aim — to evaluate the probability of stable deep MR and the rate of patients who meet the criteria for TFR observation in the Russian part of the international multicenter prospective population study EUTOS PBS (European Treatment and Outcome Study — Population-Based Study). Materials and methods. Registration of all CML cases in the EUTOS PBS was conducted in 6 regions of Russia from September 2009 to December 2012. The main inclusion criterion was the diagnosis of CML confirmed by cytogenetic or molecular study in patients aged over 18 years. In total, 197 CML patients were included: 181 (92 %) with chronic phase (CP) CML, 14 (7 %) with accelerated phase (AP) and 2 (1 %) with blast crisis (BC) at diagnosis. Data on therapy and results was updated annually. Results. Deep MR (at least MR4 or BCR::ABL1 level less than 0.01 % IS) was achieved in 104 (54 %) of 192 patients receiving TKI therapy, with a median observation period of 7 years (range from 3 months to 10 years). The probability of a deep MR after 5 years of treatment was 48 % (95 % confidence interval (95% CI): 40–55 %) in patients with CP. The cumulative incidence of a stable deep MR with duration of more than 2 years in CML CP patients was 16 % (95% CI: 11–22 %) after 5 years of therapy, 29 % (95% CI: 22–37 %) after 7 years of therapy and 50 % (95% CI: 38–60 %) after 9 years of therapy. The cumulative incidence of a stable deep MR was significantly higher in those patients who had achieved a deep MR at 36 months of therapy compared to patients with only MMR: 40 % (95% CI: 28–53 %) vs. 3 % (95% CI: 0–13 %) at 5 year of therapy; 66 % (95% CI: 52–77 %) vs. 15 % (95% CI: 5–30 %) at 7 year and 89 % (95% CI: 64–97 %) vs. 48 % (95% CI: 25–67 %) at 9 year (p < 0.0001) in patients without MMR by 36 months. No patients without MMR at 36 months of therapy subsequently gained a stable deep MR. Fifty four patients met the TKI discontinuation criteria for transition into TFR phase: CP CML with a typical BCR::ABL1 p210 transcript, TKI therapy for more than 3 years and a stable deep MR for over 2 years. The rate of possible candidates for cancellation of therapy was 28 % of all 192 patients who received TKI in the study or 31 % in terms of patients with CP CML. Predominantly, patients with low-risk by Sokal or ELTS score were among the potential TFR candidates 26 (48 %) and 33 (61 %), respectively. No patients with long-term resistance to therapy were the TFR candidates. Conclusion. In the Russian portion of the prospective observational multicenter study EUTOS PBS, it was found that with a median duration of TKI therapy of 7 years, about a third of patients with CP CML may be candidates for the controlled therapy discontinuation. If half of these patients remain in molecular remission, up to 15 % of the initial number of patients will be able to continue observation in the TFR. Achievement of MMR and deep MR at 36 months of therapy is associated with a significantly greater likelihood of meeting the criteria for follow-up in the TFR phase in the future.

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