A long-term follow- up of observation in treatment- free remission in patients with chronic myeloid leukemia

Introduction. The option of observation without therapy with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) patients is already included in Russian and international clinical guidelines. Evaluation of long-term follow-up results of treatment free remission (TFR) in CML patients is relevant for the introduction of this approach into routine clinical practice. Aim - to demonstrate the outcomes in a long-term follow-up of CML patients who discontinued TKI therapy in the RU-SKI trial. Patients and methods. The prospective study included 98 CML patients with TKI therapy duration >= 3 years and a deep molecular response (DMR, BCR::ABL1 <= 0.01 %) duration >= 2 years. TKI therapy was resumed with the loss of a major MR (MMR, BCR::ABL1 > 0,1 %). Results. Median time of follow-up after TKI discontinuation was 64 months (range of 51-86 months). Survival without MMR loss at 3 and 5 years after TKI discontinuation was 51 % (CI 41- 61 %) and 46 % (CI 36-57 %) respectively. From 3 to 5 years of follow-up without therapy, the loss of MMR occurred in 2 (4 %) patients. There was no MMR loss observed after 5 years of follow-up. In patients with first and second treatment discontinuation, survival without MMR loss was 50 % versus 12,5 % (rho = 0,039). All 50 patients with molecular relapses regained MMR and MR4 after TKI therapy resumption. BCR::ABL1 level fluctuations 0,01- 0,1 % were in 62 % (n = 29) patients, who were in TFR at the time of analysis. Loss of MR4 was observed in 38 (42 %) from 90 patients with first TKI discontinuation. Survival without MMR loss from MO4 loss was 24 % at 5 years after TKI discontinuation. Loss of MO4 in the first 3 months after TKI cessation was associated with a high probability of further MMR loss (8 % versus 54 % in patients with loss of MO4 for > 3 months, p = 0.00015). Conclusion. The low frequency of late relapses (4 % after 3 years of follow-up) and the possibility of long-term persistence of minimal residual disease (MRD) after discontinuation of therapy determine the need to optimize the timing of molecular monitoring, taking into account the MRD status of patients.