BACKGROUND: To evaluate the outcomes of first-line imatinib versus nilotinib treatment for chronic myeloid leukemia in the chronic phase (CML-CP) in real-world clinical practice. METHODS: A propensity score analysis was performed to eliminate imbalances between the treatment groups. In the analysis, 163 patients in the nilotinib group and 163 patients in the matched imatinib group were retrospectively evaluated. RESULTS: Nilotinib-treated patients achieved complete cytogenetic response (CCyR) and major molecular response more rapidly than imatinib-treated patients. However, there was no significant difference in 5-year overall survival (OS) or progression-free survival (PFS) between the two groups (OS: 94.3% vs. 90.5%, p = 0.602; PFS: 92.9% vs. 88.0%, p = 0.614). Nilotinib-treated patients had a higher failure-free survival (FFS) and event-free survival (EFS) than imatinib-treated patients (FFS: 71.7% vs. 54.3%, p = 0.040; EFS: 71.7% vs. 53.5%, p = 0.025). CONCLUSIONS: This retrospective analysis from clinical practice did not confirm any benefit of frontline nilotinib treatment for OS and PFS; however, it did demonstrate higher FFS and EFS in the nilotinib cohort.

1st Department of Internal Medicine Haematology General University Hospital and Charles University Prague Czech Republic

4th Department of Internal Medicine and Haematology University Hospital Hradec Kralove and Charles University Prague Czech Republic

Central European Institute of Technology Masaryk University Brno Czech Republic

Department of Haemato oncology University Hospital Olomouc and Palacky University Olomouc Czech Republic

Department of Haemato oncology University Hospital Ostrava and Ostrava University Ostrava Czech Republic

Department of Haemato oncology University Hospital Plzen and Charles University Plzen Czech Republic

Department of Internal Medicine Haematology and Oncology University Hospital Brno and Masaryk University Brno Czech Republic

Department of Internal Medicine Haematology University Hospital Kralovske Vinohrady and Charles University Prague Czech Republic

Institute of Biostatistics and Analyses Masaryk University Brno Czech Republic

Institute of Haematology and Blood Transfusion Prague Czech Republic

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Guilhot F, Chastang C, Michallet M, et al. Chronic myeloid leukemia study group. Interferon alfa‐2b combined with cytarabine versus interferon alone in chronic myelogenous leukemia. French. N Engl J Med. 1997;337(4):223‐229. doi:10.1056/NEJM199707243370402 PubMed DOI

Baccarani M, Rosti G, de Vivo A, et al. A randomized study of interferon‐alpha versus interferon‐alpha and low‐dose arabinosyl cytosine in chronic myeloid leukemia. Blood. 2002;99(5):1527‐1535. doi:10.1182/blood.v99.5.1527 PubMed DOI

O'Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low‐ dose cytarabine for newly diagnosed chronic‐phase chronic myeloid leukemia. N Engl J Med. 2003;348(11):994‐1004. doi:10.1056/NEJMoa022457 PubMed DOI

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. doi:10.1056/NEJMoa1609324 PubMed DOI PMC

Talpaz M, Shah NP, Kantarjian H, et al. Dasatinib in imatinib resistant Philadelphia chromosome‐positive leukemias. N Engl J Med. 2006;354(24):2531‐2541. doi:10.1056/NEJMoa055229 PubMed DOI

Radich JP, Kopecky KJ, Appelbaum FR, et al. A randomized trial of dasatinib 100 mg versus imatinib 400 mg in newly diagnosed chronic‐phase chronic myeloid leukemia. Blood. 2012;120(8):3898‐3905. doi:10.1182/blood-2012-02-410688 PubMed DOI PMC

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):2333‐2340. doi:10.1200/JCO.2015.64.8899 PubMed DOI PMC

O'Brien S, Cork L, Bandeira V, et al. Spirit 2: final 5 year analysis of the UK national cancer research institute randomized study comparing imatinib with dasatinib in patients with newly diagnosed chronic phase CML. Blood. 2018;132(Supplement 1):457. doi:10.1182/blood-2018-99-110128 PubMed DOI

Saglio G, Kim DW, Issaragrisil S, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010;362(24):2251‐2259. doi:10.1517/14656566.2011.534780 PubMed DOI

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(5):1044‐1054. doi:10.1038/leu.2016.5 PubMed DOI PMC

Kantarjian HM, Hughes TP, Richard A, et al. Long‐term outcomes with frontline nilotinib versus imatinib in newly diagnosed chronic myeloid leukemia in chronic phase: ENESTnd 10‐year analysis. Leukemia. 2021;35(2):440‐453. doi:10.1038/s41375-020-01111-2 PubMed DOI PMC

Gugliotta G, Castagnetti F, Breccia M, et al. Treatment‐free remission in chronic myeloid leukemia patients treated front‐line with nilotinib: 10‐year follow‐up of the GIMEMA CML 0307 study. Haematologica. 2022;107(10):2356‐2364. doi:10.3324/haematol.2021.280175 PubMed DOI PMC

Brummendorf TH, Cortes JE, de Souza CA, et al. Bosutinib versus imatinib in newly diagnosed chronic‐phase chronic myeloid leukaemia: results from the 24‐month follow‐ up of the BELA trial. Br J Haematol. 2015;168(1):69‐81. doi:10.1111/bjh.13108 PubMed DOI PMC

Cortes JE, Gambacorti‐Passerini C, Deininger MW, et al. Bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia: results from the randomized BFORE trial. J Clin Oncol. 2018;36(3):231‐237. doi:10.1200/JCO.2017.74.7162 PubMed DOI PMC

Hochhaus A, Baccarani M, Silver RT, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020;34(4):966‐984. doi:10.1038/s41375-020-0776-2 PubMed DOI PMC

Hehlmann R. The new ELN recommendations for treating CML. J Clin Med. 2020;9(11):3671. doi:10.3390/jcm9113671 PubMed DOI PMC

Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2022 update on diagnosis, therapy, and monitoring. Am J Hematol. 2022;97(9):1236‐1256. doi:10.1002/ajh.26642 PubMed DOI

Shah NP, Bhatia R, Altman JK, et al. Chronic myeloid leukemia, version 2.2024, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2024;22(1):43‐69. https://www.nccn.org/professionals/physician_gls/pdf/cml.pdf PubMed

Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975–2016. National Cancer Institute; 2016. https://seer.cancer.gov/csr/1975_2016/, based on November 2018 SEER data submission, posted to the SEER web site, April 2019. https://seer.cancer.gov/csr/1975_2016/

Hoffmann VS, Baccarani M, Hasford J, et al. The EUTOS population‐based registry: incidence and clinical characteristics of 2904 CML patients in 20 European countries. Leukemia. 2015;29(6):1336‐1343. doi:10.1038/leu.2015.73 PubMed DOI

Andrews CN, Lipton J. The true value of second‐generation TKIs as first‐line therapy in chronic myeloid leukaemia. Lancet Haematol. 2019;6:e385‐e386. doi:10.1016/S2352-3026(19)30112-7 PubMed DOI

Vener C, Banzi R, Ambrogi F, et al. First‐line imatinib vs second‐ and third‐generation TKIs for chronic‐phase CML: a systematic review and meta‐analysis. Blood Adv. 2020;4(12):2723‐2735. doi:10.1182/bloodadvances.2019001329 PubMed DOI PMC

Saglio G, Jabbour E. First‐line therapy for chronic phase CML: selecting the optimal BCR‐ABL1‐targeted TKI. Leuk Lymphoma. 2018;59(7):1523‐1538. doi:10.1080/10428194.2017.1379074 PubMed DOI

Senapati J, Sasaki K, Issa GC, et al. Management of chronic myeloid leukemia in 2023—common ground and common sense. Blood Cancer J. 2023;13(1):58. doi:10.1038/s41408-023-00823-9 PubMed DOI PMC

Rea D, Nicolini FE, Tulliez M, et al. Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G‐TKI study. Blood. 2017;129(7):846‐854. doi:10.1182/blood-2016-09-742205 PubMed DOI

Hughes TP, Ross DM. Moving treatment‐free remission into mainstream clinical practice in CML. Blood. 2016;128(1):17‐23. doi:10.1182/blood-2016-01-694265 PubMed DOI

Hochhaus A, Masszi T, Giles FJ, et al. Treatment‐free remission following frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the ENESTfreedom study. Leukemia. 2017;31:1525‐1531. doi:10.1038/leu.2017.63 PubMed DOI PMC

Ross DM, Masszi T, Gómez Casares MT, et al. Durable treatment‐free remission in patients with chronic myeloid leukemia in chronic phase following frontline nilotinib: 96‐week update of the ENESTfreedom study. J Cancer Res Clin Oncol. 2018;144(5):945‐954. doi:10.1007/s00432-018-2604-x PubMed DOI PMC

Rea D, Ame S, Berger M, et al. Discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia: recommendations for clinical practice from the French Chronic Myeloid Leukemia Study Group. Cancer. 2018;124(14):2956‐2963. doi:10.1002/cncr.31411 PubMed DOI

Haddad FG, Sasaki K, Issa GC, et al. Treatment‐free remission in patients with chronic myeloid leukemia following the discontinuation of tyrosine kinase inhibitors. Am J Hematol. 2022;97(7):856‐864. doi:10.1002/ajh.26550 PubMed DOI

Aichberger KJ, Herndlhofer S, Schernthaner GH, et al. Progressive peripheral arterial occlusive disease and other vascular events during nilotinib therapy in CML. Am J Hematol. 2011;86(7):533‐539. doi:10.1002/ajh.22037 PubMed DOI

Kim TD, Rea D, Schwarz M, et al. Peripheral artery occlusive disease in chronic phase chronic myeloid leukemia patients treated with nilotinib or imatinib. Leukemia. 2013;27(6):1316‐1321. doi:10.1038/leu.2013.70 PubMed DOI

Breccia M, Muscaritoli M, Gentilini F, et al. Impaired fasting glucose level as metabolic side effect of nilotinib in non‐diabetic chronic myeloid leukemia patients resistant to imatinib. Leuk Res. 2007;31:1770‐1772. doi:10.1016/j.leukres.2007.01.024 PubMed DOI

Hornak T, Semerad L, Zackova D, et al. Analysis of serum lipids, cardiovascular risk, and indication for statin use during nilotinib and imatinib therapy in de novo CML patients–results from real‐life prospective study. Leuk Lymphoma. 2020;61(2):494‐496. doi:10.1080/10428194.2019.1672054 PubMed DOI

Chow EJ, Doody DR, Wilkes JJ, et al. Adverse events among chronic myelogenous leukemia patients treated with tyrosine kinase inhibitors: a real‐world analysis of health plan enrollees. Leuk Lymphoma. 2021;62(5):1203‐1210. doi:10.1080/10428194.2020.1855340 PubMed DOI PMC

Milojkovic D, Lyon AR, Mehta P, et al. Cardiovascular risk in chronic myeloid leukaemia: a multidisciplinary consensus on screening and management. Eur J Haematol. 2023;111(2):201‐210. doi:10.1111/ejh.13983 PubMed DOI

Vener C, Rossi S, Minicozzi P, et al. The EUROCARE‐6 Working Group. Clear improvement in real‐world chronic myeloid leukemia survival: a comparison with randomized controlled trials. Front Oncol. 2022;12. doi:10.3389/fonc.2022.892684 PubMed DOI PMC

Guilhot J, Baccarani M, Clark RE, et al. Definitions, methodological and statistical issues for phase 3 clinical trials in chronic myeloid leukemia: a proposal by the European LeukemiaNet. Blood. 2012;119(25):5963‐5971. doi:10.1182/blood-2011-10-383711 PubMed DOI

Oken M, Creech R, Tormey D, et al. Toxicity and response criteria of the eastern cooperative oncology group. Am J Clin Oncol. 1982;5(6):649‐655. PubMed

Accessed March 9, 2018. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf.

Milojkovic D, Cross NC, Ali S, et al. Real‐world tyrosine kinase inhibitor treatment pathways, monitoring patterns and responses in patients with chronic myeloid leukaemia in the United Kingdom: the UK TARGET CML study. Br J Haematol. 2021;192(1):62‐74. doi:10.1111/bjh.16733 PubMed DOI

Canet J, Cony‐Makhoul P, Orazio S, et al. Second‐ or third‐generation tyrosine kinase inhibitors in first‐line treatment of chronic myeloid leukemia in general population: is there a real benefit? Cancer Med. 2021;10(20):6959‐6970. doi:10.1002/cam4.4186 PubMed DOI PMC

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):1648‐1671. doi:10.1038/leu.2016.104 PubMed DOI PMC

Jain P, Kantarjian H, Boddu PC, et al. Analysis of cardiovascular and arteriothrombotic adverse events in chronic‐phase CML patients after frontline TKIs. Blood Adv. 2019;3(6):851‐861. doi:10.1182/bloodadvances.2018025874 PubMed DOI PMC

Cirmi S, El Abd A, Letinier L, et al. Cardiovascular toxicity of tyrosine kinase inhibitors used in chronic myeloid leukemia: an analysis of the FDA adverse event reporting system database (FAERS). Cancers (Basel). 2020;12(4):826. doi:10.3390/cancers12040826 PubMed DOI PMC

Saussele S, Krauss MP, Hehlmann R, et al. Impact of comorbidities on overall survival in patients with chronic myeloid leukemia: results of the randomized CML study IV. Blood. 2015;126(1):42‐49. doi:10.1182/blood-2015-01-617993 PubMed DOI PMC

Gunnarsson N, Sandin F, Höglund M, et al. Population‐based assessment of chronic myeloid leukemia in Sweden: striking increase in survival and prevalence. Eur J Haematol. 2016;97(4):387‐392. doi:10.1111/ejh.12743 PubMed DOI

Breccia M, Luciano L, Latagliata R, et al. Age influences initial dose and compliance to imatinib in chronic myeloid leukemia elderly patients but concomitant comorbidities appear to influence overall and event‐free survival. Leuk Res. 2014;38(10):1173‐1176. doi:10.1016/j.leukres.2014.06.020 PubMed DOI

Bower H, Björkholm M, Dickman PW, Höglund M, Lambert PC, Andersson TM. Life expectancy of patients with chronic myeloid leukemia approaches the life expectancy of the general population. J Clin Oncol. 2016;34(24):2851‐2857. doi:10.1200/JCO.2015.66.2866 PubMed DOI

Giai V, Stagno F, Rosso T, et al. The use of 2nd generation TKIs As first line therapy does not prevent CML related deaths: results of an Italian CML campus prospective study in 1277 patients treated first line with imatinib or 2nd generation TKIs. Blood. 2023;142(Supplement 1):3168.