Clinical efficacy and safety of first-line nilotinib or imatinib therapy in patients with chronic myeloid leukemia-Nationwide real life data.
Humans
Imatinib Mesylate
/ therapeutic use
Pyrimidines
/ therapeutic use
Female
Male
Middle Aged
Retrospective Studies
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
/ drug therapy
Adult
Aged
Treatment Outcome
Antineoplastic Agents
/ therapeutic use
Protein Kinase Inhibitors
/ therapeutic use
Propensity Score
Progression-Free Survival
Young Adult
chronic myeloid leukemia
first‐line treatment
imatinib
nilotinib
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
Sep 2024
Sep 2024
Historique:
revised:
31
07
2024
received:
16
02
2024
accepted:
18
08
2024
medline:
15
9
2024
pubmed:
15
9
2024
entrez:
13
9
2024
Statut:
ppublish
Résumé
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. 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. 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). 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.
Sections du résumé
BACKGROUND
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
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
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
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.
Substances chimiques
nilotinib
F41401512X
Imatinib Mesylate
8A1O1M485B
Pyrimidines
0
Antineoplastic Agents
0
Protein Kinase Inhibitors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e70158Subventions
Organisme : The project National Institute for Cancer Research The project National Institute for Cancer Research
ID : LX22NPO5102
Organisme : DRO and the Cooperatio Program
ID : 00179906
Informations de copyright
© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.
Références
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Hehlmann R. The new ELN recommendations for treating CML. J Clin Med. 2020;9(11):3671. doi:10.3390/jcm9113671
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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.
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
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
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
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
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
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
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
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
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
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.