CML-231 Long-Term Results of Tyrosine Kinase Inhibitors Discontinuation in Patients With Chronic Myeloid Leukemia

Abstract

Evaluation of long-term follow-up results of treatment-free remission (TFR) in chronic myeloid leukemia (CML) patients is relevant for the introduction of this approach into routine clinical practice. To analyze the outcomes in a long-term follow-up of a Russian cohort of CML patients who discontinued tyrosine kinase inhibitors (TKI) therapy. TKI treatment was discontinued in 185 CML patients with deep molecular response (DMR, at least MR4, BCR::ABL1≤0.01% IS, duration ≥1 year), including 113 patients in the prospective RU-SKI trial and 72 patients in the retrospective group out of the trial. Molecular relapse and TKIs restart was in the case of major MR (MMR, BCR::ABL1>0.1%) loss. In pregnant patients, TKIs were restarted in case of MR2 (BCR::ABL1>1%) loss. Baseline Characteristics: Male 39%, the median age was 43 (21-86) years. Imatinib and second-generation TKIs (2G TKIs) were in 124(67%) and 61(63%) patients accordingly. The median duration of TKI therapy was 83 (6-218) months. The second discontinuation was in 8 patients. Median time of follow-up without therapy was 6 years. Therapy was resumed in 96 (52%) patients with MMR loss and in 6 (3.2%) patients without MMR loss (DMR loss, withdrawal syndrome). Seven (3.8%) patients have died (not related to CML). In total, 80 (43%) patients remained in TFR. Survival without therapy at 2 and 5 years after TKI discontinuation was 48% (CI 41-55%) and 42% (CI 34-49%) respectively. In patients with first and second discontinuation survival without therapy was 43% versus 12.5% (p=0.036). The cumulative incidence of MMR loss 5 years after TKI discontinuation was 53% (95% CI 47-59%). Loss of MMR between 1 and 3 years after TKI stop was in 9 patients, between 3 and 5 years - in 6 patients. There was no MMR loss after 57 months of follow-up. After 5 years of follow-up BCR::ABL1 level fluctuations 0.01-0.1% were in 4 (5%) patients. The probability of MMR loss after 5 years of follow-up was 53%. Molecular relapses were rare after 2 years without TKI therapy. However, molecular monitoring with a frequency of 2-3 times a year during long-term observation in TFR is mandatory for patients' safety, especially in those with detectable MRD.