Single Center Study of Prescribing and Treatment Outcomes of Patients with Chronic Myeloid Leukemia
Background: The present study investigated the patients with Chronic Myeloid Leukemia in chronic phase (CP-CML) who had beenon the first- line Imatinib Mesylate (IM) therapy for a period of 84 months.
Materials and Methods: This retrospective study was conducted in 295 newly-diagnosed CP-CML patients(age >18 years)who were admitted to the Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran during 1 January 2009 to 30 December 2016. Response to treatment was evaluated by molecular response assessment. Rates of IM dose adjustment, switching to another drug therapy, Progression to Accelerate Phase (AP) and Blastic Crisis (BC) and long-term outcomes included Overall Survival (OS) and Progression Free Survival (PFS) were assesed.
Results: Patients’ average age was 41.7 years, and 52.9% were male. 44.4% of patients at the month 18 achieved Major Molecular Response (MMR). Progression to AP/BC occurred in 26 patients during 84 months, and the estimated rate of OS and PFS were 71.83 and 74.48, respectively. Among the patients who didn’t achieve MMR at month 18 , 61 patients were treated with IM ( 400 mg /day), and then after month 18, 24(39.3%) of whom achieved MMR. Dose adjustments occurred in 60 patients (20.33%). IM dose increases were observed in 53 patients who didn’t achive optimal response to imatinib or loss of optimal response. IM dose decreases were observed in 7 patients. 25 (8.47%) patients were switched to a different Tyrosine Kinase Inhibitor (TKI). Most of TKI changes(n=21) happened in patients who didn’t achieve optimal response to IM and for the 4 patients TKI changes were owing to adverse events of IM. Among the patients undergoing change in treatment, 24(43.75%) patient achieved MMR.
Conclusion: Our data showed the high effectiveness of the change in the treatment of IM-resistant condition. Moreover, our finding suggests that imatinib be effective in Iranian patients after a long period of time compared to the referenced studies.
2. Hehlmann R, Hochhaus A, Baccarani M, et al. Chronic myeloid leukaemia. Lancet. 2007. 370(9584): 342-350.
3. Höglund M, Sandin F, Simonsson B. Epidemiology of chronic myeloid leukaemia: an update. Ann Hematol. 2015; 94 Suppl 2:S241-7.
4. Hochhaus A, Saussele S, Rosti G, et al., Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017; 28(suppl_4):iv41-iv51.
5. Mendizabal AM, Garcia-Gonzalez P, Levine PH. Regional variations in age at diagnosis and overall survival among patients with chronic myeloid leukemia from low and middle income countries. Cancer Epidemiol. 2013; 37(3):247-54
6. Baccarani M, Castagnetti F, Gugliotta G, et al., A review of the European LeukemiaNet recommendations for the management of CML. Ann Hematol. 2015; 94 Suppl 2:S141-7.
7. Hughes TP, Hochhaus A, Branford S, et al. Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS). Blood. 2010; 116(19): 3758-3765.
8. Hochhaus A, Larson RA, Guilhot F, et al. Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N Engl J Med. 2017; 376(10):917-927
9. Chahardouli B, Zaker F, Mousavi SA, et al. Evaluation of T315I mutation frequency in chronic myeloid leukemia patients after imatinib resistance. Hematology. 2013; 18(3):158-62.
10. Steegmann JL, Baccarani M, Breccia M, et al. European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia. Leukemia. 2016; 30(8):1648-71
11. Nekoohesh L, Rostami S, Nikbakht M, et al. Evaluation of Molecular Response to Imatinib Mesylate Treatment in Iranian Patients With Chronic Myeloid Leukemia. Clin Lymphoma Myeloma Leuk. 2019.
12. Chahardouli B, Zaker F, Mousavi SA, et al. Detection of BCR-ABL kinase domain mutations in patients with chronic myeloid leukemia on imatinib. Hematology. 2013; 18(6): 328-33.
13. Eden, R.E. and J.M. Coviello. Cancer, Leukemia, Myelogenous, Chronic (CML, Chronic Granulocytic Leukemia), in StatPearls. 2018, StatPearls Publishing LLC: Treasure Island FL.
14. Guru Murthy GS, Atallah E. Treatment-Free Remission in CML: the US Perspective. Curr Hematol Malig Rep. 2019; 14(1):56-61.
15. Jabbour E, Saglio G, Hughes TP, et al. Suboptimal Responses in Chronic Myeloid Leukemia. Cancer. 2012; 118(5): 1181–1191.
16. Jabbour EJ, Cortes JE, Kantarjian HM.Kantarjian, Resistance to Tyrosine Kinase Inhibition Therapy for Chronic Myelogenous Leukemia: A Clinical Perspective and Emerging Treatment Options. Clin Lymphoma Myeloma Leuk. 2013; 13(5):515-29.
17. Rossari F, Minutolo F, Orciuolo E. Past, present, and future of Bcr-Abl inhibitors: from chemical development to clinical efficacy. J Hematol Oncol. 2018; 11(1):84.
18. Bhamidipati PK, Kantarjian H, Cortes J, et al. Management of imatinib-resistant patients with chronic myeloid leukemia. Ther Adv Hematol. 2013; 4(2):103-17.
19. Baccarani, M., et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia. 2013. Blood; 122(6): 872-884.