Retrospective analysis of tyrosine kinase inhibitor molecules used in the second and third line treatment of chronic myeloid leukemia patients in terms of efficacy, side effects and survival

Chronic Myeloid Leukemia (CML); it is a myeloproliferative disorder characterized by pathological clonal proliferation of pluripotent hematopoietic stem cells as a result of increased tyrosine kinase activity. CML accounts for approximately 15-20% of adult leukemias. In the world of tyrosine kinase inhibitors, the goal of CML treatment is normal survival time and good quality of life. The aim of this study; response rates of patients with chronic myeloid leukemia in first-line treatment, rates of switching to second and third-line TKI treatment after first-line treatment, factors affecting the number of TKI steps; It was aimed to retrospectively examine nilotinib and dasatinib treatments in terms of efficacy, side effects, survival, molecular response depth and molecular remission period in second-line therapy. Between January 1, 2002 and June 1, 2022, 105 patients followed by Hacettepe University Hospital Department of Hematology with the diagnosis of chronic myeloid leukemia were included in the study. In our study, the median follow-up period with the diagnosis of CML was calculated as 89(2-334) months. At the time of diagnosis, 102 (97.1%) patients were diagnosed in the chronic phase, 2 (2%) patients in the accelerated phase, and 1 (1%) patient in the blastic phase. It was determined that 3 (2.9%) of 105 patients transitioned to the accelerated phase during the treatment and follow-up period, and it was observed that 3 (2.9%) patients progressed to the blastic phase during the follow-up period. The 5-year survival rate in our CML study patients was calculated as 96.8%  0.019. During the follow-up, death from any cause occurred in 6 (5.7%) patients. When the relationship between prognostic scoring systems and overall survival in CML patients was examined, a statistically significant relationship was found between ELTS risk groups and overall survival (p:0.003). Overall survival tended to be worse in patients in the group with a high ELTS risk score. No statistically significant correlation was found between the Sokal, Hasford and EUTOS risk groups and overall survival. Of the 105 patients included in the study, 61 (58%) were followed in remission with first-line imatinib treatment, and 43 (40.9%) patients were switched to second-line TKI treatment. It was observed that 14 (13.3%) patients were switched to third line TKI treatment. A statistically significant difference was found between the presence of variant Ph chromosome and the number of TKI steps at diagnosis (p:0.029), and it was observed that all patients with variant Ph chromosome were switched to second-line TKI treatment. No statistically significant correlation was found between the Hasford, Sokal, EUTOS, ELTS risk groups calculated at diagnosis and the number of TKI steps. A statistically significant difference was found between the molecular unresponsiveness at the 3rd and 6th months in the first-line TKI treatment and the number of TKI steps (p:0.014, p<0.001, respectively). It was observed that 26 (60.5%) patients received dasatinib and 17 (39.5%) nilotinib treatment in the second-line treatment. In the second-line treatment, the median follow-up time with dasatinib was 39(3-102) months, and the median follow-up time with nilotinib was 36(2-85) months. A statistically significant difference was found between dasatinib and nilotinib treatments in favor of dasatinib in terms of early molecular response in second-line TKI treatment. There was no significant difference between dasatinib and nilotinib treatments in terms of the rates of reaching MR 4.0 and MR 4.5 responses in the second line treatment, and the time to reach MR 4.0 and MY 4.5 responses. In conclusion, dasatinib and nilotinib have similar efficacy in the second-line treatment of CML, and the ELTS risk scoring system is more successful than other scoring systems in predicting the overall survival of CML patients.