CML-155 Prognostic Markers of the Effectiveness of Tyrosine Kinase Inhibitors in Third-Line Therapy of Chronic Phase Chronic Myeloid Leukemia Patients: Data From a Multicenter Study

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Despite success in chronic myeloid leukemia (CML) treatment there are unmet needs third-line therapy. To determine the efficacy and factors influencing the long-term outcomes of third-line therapy with tyrosine kinase inhibitors (TKIs). Multicenter retrospective study was conducted in 2019. All adult 73 pts, including 26(35%), CML chronic phase (CP) pts treated with TKIs in third line (TKI-3L) without complete cytogenetic response (CCyR) at baseline were included in the study. The me duration of CML from diagnosis to baseline was 63(10-314) mos. The rate of CCyR (equal to BCR::ABL transcript level <1%) and overall survival (OS) were assessed. Univariate and multivariate logistic regression analyses assessed risk factors for CCyR achievement. For a scoring system, selection of predictors was performed using L2-regularization after standardization of quantitative variables. The me duration of TKI-3L therapy was 14(1-120) mos, the me time of follow-up from initiation of TKI-3L was 25(3-136) mos. CCyR was achieved in 22/73(30%) pts. Both in univariate and multivariate regression analysis factors influenced on CCyR achievement were absence of CCyR at baseline (OR 0.26[95% CI, 0.08-0.85]; p=0.0252), no CCyR on TKI-1L and TKI-2L (OR 0.21[95% CI, 0.04-0.99]; p=0.0502), as well as pt's age at baseline per every 10 years (OR 1.52[95% CI, 0.61-3.8]; p=0.369). Score system was set up based on these factors with scores 7, 8, 1 score per 10 years respectively. ROC analysis divided pts into three groups: low risk (score ≤9, n=22), intermediate-risk (score 10-15, n=27) and high risk (score ≥16, n=24). The low-risk group had a significantly higher rate of CCyR on TKI-3L compared to intermediate or high-risk groups (14/22[64%] vs 7/27[26%] vs 1/24[4%], p<0.05). There were 19(26%) deaths. Estimated 1-year and 5-year OS was 95% and 65% respectively. All CML-related deaths(n=14), as well as transformation to BC (n=13), occurred in intermediate- and high-risk groups. Nearly a third of pts obtained CCyR on TKI-3L in our study. Most pts were alive at 5 years. Younger pts with any CyR on previous TKIs and at baseline had favorable prognosis. The use of TKI-3L is justified in low-risk groups and may be used in transplant-eligible pts.