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Abstract
The development of TKIs has meant a big step in oncohematology leading to a normal life expectancy in CML patients. Adherence is a requirement to achieve sustained deep responses. Adverse events (AE) may compromise the continuity of treatment by interfering with QoL, precluding optimal outcomes. Deep knowledge of ITKs´ toxicity is essential in daily medical practice in order to manage AE and favor patient´s compliance. Although data regarding the development of second malignancies are contradictory, they are among the most common causes of death in this population. Methods. We performed a prospective study of 79 patients with CML diagnosis treated with first and second generation TKIs. Toxicity was evaluated according to CTCAE v5. We recorded the development of second malignancies, the association between age and treatment withholding due to toxicity, and the probability of optimal outcome in patients in whom AE led to treatment interruption. In the group receiving dasatinib we studied the association between lymphocytosis and the development of AE (diarrhea and pleural effusion), and with the probability of achieving an optimal response. Results. The observed toxicity of ITKs was similar to previous reports. There were no hematologic AE beyond the third month of treatment. Five second malignancies were recorded, leading to death in three patients, all of them with complete cytogenetic response. Dose reduction and treatment interruption did not relate to age (above or under 60). Treatment withholding affected the therapeutic goal (optimal response) only in patients receiving imatinib. The small number of patients treated with second generation TKIs may explain the lack of impact in this group. Development of dasatinib-associated lymphocytosis was not a risk factor for toxicity or optimal response.
References
2. Hehlmann R, Lauseker M, SauɃele S et al. Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants. Leukemia. 2017; 31:2398.
3. Hanfstein B, Müller M et al. for the SAKK and the German CML Study Group. Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML). Leukemia. 2012; 26:2096-2102.
4. Hanfstein B, Müller MC & Hochhaus A. Response-related predictors of survival in CML. Ann Hematol. 2015; 94 (Suppl 2): 227.
5. Falchi L, Kantarjian H, Wang X et al. Significance of deeper molecular responses in patients with chronic myeloid leukemia in early chronic phase treated with tyrosine kinase inhibitors. Am J of Hemat. 2013; 88 (12): 1024-29.
6. Baccarani M, Cortes J, Pane F et al (European Leukemia Net). Chronic myeloid leukemia: an update of concepts and management recommendations of European Leukemia Net. J Clin Oncol. 2009; 27(35): 6041-51.
7. Baccarani M, Deininger, M Rosti G et al. European Leukemia Net recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013; 122(6): 872-884.
8. Baccarani M, Castagnetti F, Gugliotta et al. A review of the European LeukemiaNet recommendations for the management of CML. Ann Hematol. 2015; 94(Suppl 2):S141-S147.
9. O’Brien S, Guilhot F, Larson R. Imatinib Compared with Interferon and Low-Dose Cytarabine for Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia. N Engl J Med. 2003. 348:994-1004.
10. Cortes JE; Saglio G; Kantarjian HM et al. Final 5-Year Study Results of DASISION: The Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients Trial. J Clin Oncol. 2016;34 (20): 2333-40.
11. Hochhaus A, Saglio G, Hughes TP et al. Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial. Leukemia. 2016; 30:1044-54.
12. Rea D. Management of adverse events associated with tyrosine kinase inhibitors in chronic myeloid leukemia. Ann Hematol. 2015; 94(Suppl 2): S149-S158.
13. Steegmann JL, Baccarani M, Breccia M. European Leukemia Net recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia. Leukemia. 2016 Aug; 30(8):1648-71.
14. Baccarani M, Saglio G, Goldman J et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European Leukemia Net. Blood. 2006;108:1809-20.
15. Paydas S. Dasatinib, large granular lymphocytosis, and pleural effusion: useful or adverse effect? Crit Rev Oncol Hematol. 2014; 89(2):242-7.
16. Mustjoki S, Laurinolli T, Ekblom M et al. Clonal Large Granular Lymphocyte (LGL) Expansion Associated with Dasatinib Therapy. Blood. 2007;110:2938.
17. Nagata Y, Ohashi K. Clinical features of dasatinib-induced large granular lymphocytosis and pleural effusion. International Journal of Hematology. 2010;91 (5):799.
18. Barreto Miranda M, Lauseker M, Proete U. Secondary Malignancies in CML Patients - Data From the German CML Study IV. Blood. 2012; 120:3746.
19. Rebora P, Czene K, Antolini L et al. Are Chronic Myeloid Leukemia Patients More at Risk for Second Malignancies? A Population-based Study. American Journal of Epidemiology. 2010;172 (9):1028-33.
20. Gugliotta G, Castagnetti F, Breccia M et al. Incidence Of Second Primary Malignancies And Related Mortality In Imatinib-Treated Chronic Myeloid Leukemia Patients. Haematologica. 2017; 102 (9) 1530-36.
21. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf
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