Long-Term Safety and Efficacy of Imatinib in Chronic Myeloid Leukemia: Real-World Evidence from a Single-Center Study

Abstract

Objective: Imatinib mesylate, a tyrosine kinase inhibitor (TKI), has revolutionized CML treatment, improving patient survival to levels comparable to the general population. This study evaluates treatment response, side effects, and survival rates in CML patients followed at our clinic. Materials and Methods: A retrospective analysis was conducted on 76 CML patients treated with imatinib at ………. University Hospital between August 2000 and April 2022. Treatment responses, side effects, and survival outcomes were assessed. Results: The median age of patients was 49 years, with 93.4% in the chronic phase and 6.6% in the accelerated phase. Patients achieving MMR at the 6th month had significantly longer event-free survival (EFS) (198.09 ± 12.39 months; p<0.0001). The 10-year overall survival (OS) rate was 94.2%, and the 5-year OS rate was 98.5%. A total of 46.05% of patients were switched to second-generation TKIs due to insufficient response or side effects. Cox regression analysis revealed that older age at diagnosis increased the risk of death, and failure to achieve MMR at the 12th month raised event risk by 76-fold. During treatment, 30.3% of patients experienced imatinib-related side effects, with serious side effects observed in 9.2% of patients. Conclusion: Imatinib remains a highly effective and well-tolerated treatment for CML in real-world settings. The outcomes observed in this study aligned similarly with those reported in international clinical trials. Achieving early molecular responses significantly improves long-term survival. These findings underscore the importance of adherence to treatment protocols and regular monitoring.

Keywords

• Chronic Myeloid Leukemia
• Imatinib
• Major Molecular Response
• Survival

References

1. Faderl S, Talpaz M, Estrov Z, O’Brien S, Kurzrock R, Kantarjian HM. The biology of chronic myeloid leukemia. N Engl J Med. 1999;341:164–172.
2. Sokal JE, Cox EB, Baccarani M, Tura S, Gomez GA, Robertson JE et al. Prognostic Discrimination in “Good-Risk” Chronic Granulocytic Leukemia. Blood. 1984;63:789–799.
3. Hasford J, Baccarani M, Hoffmann V, Guilhot J, Saussele S, Rosti G et al. Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: The EUTOS score. Blood. 2011;118:686–692.
4. Bower H, Björkholm M, Dickman PW, Höglund M, Lambert PC, Andersson TM-L. Life expectancy of patients with chronic myeloid leukemia approaches the life expectancy of the general population. J Clin Oncol Off J Am Soc Clin Oncol. 2016;34:2851–2857.
5. Hochhaus A, Larson RA, Guilhot F, Radich JP, Branford S, Hughes TP et al. Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N Engl J Med. 2017;376:917–927.
6. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–2405.
7. Hughes T, Deininger M, Hochhaus A, Branford S, Radich J, Kaeda J et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: Review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood. 2006;108:28–37.
8. Alaggio R, Amador C, Anagnostopoulos I, Attygalle AD, Araujo IB de O, Berti E et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours: Lymphoid neoplasms. Leukemia. 2022;36:1720–1748.

9. Hochhaus A, Baccarani M, Silver RT, Schiffer C, Apperley JF, Cervantes F et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020;34:966–984.
10. Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. U.S. Department of Health and Human Services. Published November 27, 2017. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf
11. Cross NCP, White HE, Colomer D, Ehrencrona H, Foroni L, Gottardi E et al. Laboratory recommendations for scoring deep molecular responses following treatment for chronic myeloid leukemia. Leukemia. 2015;29:999–1003.
12. Claudiani S, Apperley JF. The argument for using imatinib in CML. Hematol (United States). 2018;2018:161–167.
13. Saydam G, Unal A, Haznedaroglu IC, Hacihanifioglu A, Mehtap O, Kurtoglu E et al. Turkey Real-Life Data: Demographic Features, Treatment Results and Effects of Comorbidities in Chronic Myeloid Leukemia. Int J Hematol Oncol. 2022;11:IJH40.
14. Szczepanek E, Chukwu O, Kamińska M, Wysogląd H, Cenda A, Zawada M et al. Long-term outcomes of patients with Chronic Myeloid Leukemia who commenced treatment with imatinib: A 20-year single-centre experience. Leuk Lymphoma. 2022;63:2213–2223.
15. Noens L, van Lierde M-A, De Bock R, Verhoef G, Zachée P, Berneman Z et al. Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: The ADAGIO study. Blood. 2009;113:5401–5411.
16. Signorovitch J, Ayyagari R, Reichmann WM, Wu EQ, Chen L. Major molecular response during the first year of dasatinib, imatinib or nilotinib treatment for newly diagnosed chronic myeloid leukemia: A network meta-analysis. Cancer Treat Rev. 2014;40:285–292.
17. Jabbour E, Kantarjian HM, Saglio G, Steegmann JL, Shah NP, Boqué C et al. Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION). Blood. 2014;123:494–500.
18. Kantarjian HM, Hochhaus A, Saglio G, De Souza C, Flinn IW, Stenke L et al. Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial. Lancet Oncol. 2011;12:841–851.
19. Morgan J, DeBoer RJ, Bigirimana JB, Nguyen C, Ruhangaza D, Paciorek A et al. A ten-year experience of treating chronic myeloid leukemia in rural Rwanda: Outcomes and insights for a changing landscape. JCO Glob Oncol. 2022;8:1–10.
20. Lipton JH, Chuah C, Guerci-Bresler A, Rosti G, Simpson D, Assouline S et al. Ponatinib versus imatinib for newly diagnosed chronic myeloid leukaemia: An international, randomised, open-label, phase 3 trial. Lancet Oncol. 2016;17:612–621.
21. Gambacorti-Passerini C, Cortes JE, Lipton JH, Dmoszynska A, Wong RS, Rossiev V et al. Safety of bosutinib versus imatinib in the phase 3 BELA trial in newly diagnosed chronic phase chronic myeloid leukemia. Am J Hematol. 2014;89:947–953.
22. Hochhaus A, Saglio G, Hughes TP, Larson RA, Kim D-W, Issaragrisil S 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;30:1044–1054.
23. Cortes JE, Saglio G, Kantarjian HM, Baccarani M, Mayer J, Boqué C 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 Off J Am Soc Clin Oncol. 2016;34:2333–2340.