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SIMPLICITY, Chronic-Phase Chronic Myeloid Leukaemia, Response Monitoring, TKI switching patterns, Italy
While tyrosine kinase inhibitors (TKIs) have transformed CP-CML management, limited data exist on their use in clinical practice.
SIMPLICITY (NCT01244750) is an observational study in CP-CML patients, exploring first?line (1L) TKI use and management patterns in the US and Europe. Over half of the patients recruited in Europe are from Italy (n=266). This is an analysis of the Italian cohort and a comparison with the rest of the European SIMPLICITY population. Baseline demographic, factors influencing choice of first-line TKI, response monitoring patterns and predictors of monitoring, and treatment interruptions, discontinuations and switching by index TKIs are presented for the Italian cohort in the first year of treatment and compared with that for the overall European SIMPLICITY cohort.
Italian patients received 1L imatinib (IM; retrospective [(n=31]; prospective [n=106]), dasatinib (DAS; n=56) or nilotinib (NIL; n=73). Documented cytogenetic response monitoring by 12 months was lower than expected, but almost all patients had documented molecular response monitoring. Fewer patients discontinued first-line TKI by 12 months in Italy compared with the rest of the European SIMPLICITY population (p=0.003). Of those with ?12 months follow-up since start of 1L TKI, only 7.1% (n=19) of Italian patients switched to a second-line TKI, a third less than in the rest of the European SIMPLICITY population. Of interest, intolerance as opposed to resistance, was the main reason for switching.
This analysis provides valuable insights into management and treatment patterns in Italian patients with CML within routine clinical practice.
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2. Jabbour, E, G Saglio, J RadichH Kantarjian, Adherence to BCR-ABL inhibitors: issues for CML therapy. Clin Lymphoma Myeloma Leuk. 2012;12(4):223–9.
3. Gambacorti-Passerini, C, L Antolini, F-X Mahon, F Guilhot, M Deininger, C Fava, A Nagler, C Della Casa, E Morra, E Abruzzese, A D’Emilio, F Stagno, P le Coutre, R Hurtado-Monroy, V Santini, B Martino, F Pane, A Piccin, P Giraldo, S Assouline, M Durosinmi, O Leeksma, E Pogliani, M Puttini, E Jang, J Reiffers, M ValsecchiD-W Kim, Multicenter Independent Assessment of Outcomes in Chronic Myeloid Leukemia Patients Treated With Imatinib. Journal of the National Cancer Institute. 2011;103(7):553–561.
4. Huang, X, J CortesH Kantarjian, Estimations of the increasing prevalence and plateau prevalence of chronic myeloid leukemia in the era of tyrosine kinase inhibitor therapy. Cancer. 2012;118(12):3123–3127.
5. Sasaki, K, SS Strom, S O'Brien, E Jabbour, F Ravandi, M Konopleva, G Borthakur, N Pemmaraju, N Daver, P Jain, S Pierce, H KantarjianJE Cortes, Relative survival in patients with chronic-phase chronic myeloid leukaemia in the tyrosine-kinase inhibitor era: analysis of patient data from six prospective clinical trials. The Lancet Haematology. 2015;2(5):e186–e193.
6. Baccarani, M, MW Deininger, G Rosti, A Hochhaus, S Soverini, JF Apperley, F Cervantes, RE Clark, JE Cortes, F Guilhot, H Hjorth-Hansen, TP Hughes, HM Kantarjian, DW Kim, RA Larson, JH Lipton, FX Mahon, G Martinelli, J Mayer, MC Muller, D Niederwieser, F Pane, JP Radich, P Rousselot, G Saglio, S Saussele, C Schiffer, R Silver, B Simonsson, JL Steegmann, JM GoldmanR Hehlmann, European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122(6):872–84.
7. National Comprehensive Cancer Network (NCCN). NCCN Guidelines Chronic Myelogenous Leukemia Version 1.2016. 2016 [cited 2017 May]; Available from: http://www.nccn.org/professionals/physician_gls/pdf/cml.pdf.
8. Abruzzese, E, M BrecciaR Latagliata, Second-generation tyrosine kinase inhibitors in first-line treatment of chronic myeloid leukaemia (CML). BioDrugs. 2014;28(1):17–26.
9. Baccarani, M, G Saglio, J Goldman, A Hochhaus, B Simonsson, F Appelbaum, J Apperley, F Cervantes, J Cortes, M Deininger, A Gratwohl, F Guilhot, M Horowitz, T Hughes, H Kantarjian, R Larson, D Niederwieser, R SilverR Hehlmann, Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2006;108(6):1809–20.
10. Sundar, HJ Radich, Optimizing Patient Care in Chronic Phase Chronic Myelogenous Leukemia: A Multidsciplinary Approach. Journal of the National Comprehensive Cancer Network : JNCCN. 2016;14(Supplement 1):S1–S6.
11. Goldberg, SL, J Cortes, C Gambacorti-Passerini, R Hehlmann, HJ Khoury, M Michallet, R Paquette, B Simonsson, T Zyczynski, A Foreman, E Abruzzese, D Andorsky, A Beeker, P Cony-Makhoul, R Hansen, E Lomaia, E OlavarriaM Mauro, First-line treatment selection and early monitoring patterns in chronic phase-chronic myeloid leukemia in routine clinical practice: SIMPLICITY. Am J Hematol. 2017;92(11):1214–1223.
12. Hehlmann, R, J Cortes, C Gambacorti-Passerini, SL Goldberg, HJ Khoury, M Mauro, M Michallet, H Mohamed, R Paquette, B Simonsson, M Subar, M TurnerT Zyczynski. Tyrosine kinase inhibitor (tki) switching: Experience from simplicity, a prospective observational study of chronic-phase chronic myeloid leukemia (cp-cml) patients in clinical practice. in 19th Congress of the European Hematology Association (EHA). 2014. Milan, Italy.
13. Bollu, V, A Quintas-Cardama, M Flamm, M Lill, M Thirman, F Ravandi-Kashani, LP AkardM Talpaz, PCN12 Resource utilization and perceptions of major molecular response in chronic myeloid leukemia (CML): results of a Delphi panel study. Value in Health. 2011;14:A156–A157.
14. Chen, L, A Guérin, J Xie, EQ Wu, AP Yu, SG EricsonE Jabbour, Monitoring and switching patterns of patients with chronic myeloid leukemia treated with imatinib in community settings: a chart review analysis. Curr Med Res Opin. 2012;28(11):1831–9.
15. Goldberg, SL, L Chen, A Guerin, AR Macalalad, N Liu, M Kaminsky, SG EricsonEQ Wu, Association between molecular monitoring and long-term outcomes in chronic myelogenous leukemia patients treated with first line imatinib. Curr Med Res Opin. 2013;29(9):1075–82.
16. Hanfstein, B, MC Müller, R Hehlmann, P Erben, M Lauseker, A Fabarius, S Schnittger, C Haferlach, G Gohring, U Proetel, HJ Kolb, SW Krause, WK Hofmann, J Schubert, H Einsele, J Dengler, M Hanel, C Falge, L Kanz, A Neubauer, M Kneba, F Stegelmann, M Pfreundschuh, CF Waller, S Branford, TP Hughes, K Spiekermann, GM Baerlocher, M Pfirrmann, J Hasford, S SausseleA Hochhaus, Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML). Leukemia. 2012;26(9):2096–102.
17. Marin, D, AR Ibrahim, C Lucas, G Gerrard, L Wang, RM Szydlo, RE Clark, JF Apperley, D Milojkovic, M Bua, J Pavlu, C Paliompeis, A Reid, K Rezvani, JM GoldmanL Foroni, Assessment of BCR-ABL1 transcript levels at 3 months is the only requirement for predicting outcome for patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors. J Clin Oncol. 2012;30(3):232–8.
18. Stanek, E, RE Aubert, C Sanders, FW Frueh, J Yao, RS EpsteinI Medco Health Solutions, Franklin Lakes, NJ, Inadequate BCR-ABL monitoring in imatinib-treated patients with chronic myelogenous leukemia. Journal of Clinical Oncology. 2009;27(Suppl)(15s):7077.
19. Henk, HJ, M Woloj, M ShapiroJ Whiteley, Real-world analysis of tyrosine kinase inhibitor treatment patterns among patients with chronic myeloid leukemia in the United States. Clin Ther. 2015;37(1):124–33.
20. Rashid, N, HA Koh, K Lin, C DimaanoE Felber, Real World Treatment Patterns in Chronic Myeloid Leukemia Patients Treated with Tyrosine Kinase Inhibitors in First Line in an Integrated Healthcare System. Blood. 2015;126:5157.
21. Sail, KR, L Chen, J Jackson, SG Ericson, S Haislip, T Ibison, J GilmoreMN Saleh, Treatment Patterns Among Patients with Philadelphia Chromosome Positive Chronic Myeloid Leukemia (Ph+ CML) Treated with Imatinib in a Community Setting. Blood. 2012;120(21):3179.
22. Vander Velde, N, L Chen, A Guo, H Sharma, M Marynchenko, EQ Wu, J Liu, H YangL Shi, Study of imatinib treatment patterns and outcomes among US veteran patients with Philadelphia chromosome-positive chronic myeloid leukemia. J Oncol Pract. 2013;9(5):e212-9.
23. Chen, L, D Latremouille-Viau, A Guerin, R NitulescuP Gagnon-Sanschagrin. Treatment Patterns and Healthcare Costs in Newly Diagnosed Patients with Chronic Myeloid Leukemia Receiving Dasatinib or Nilotinib As First-Line Therapy in the United States: A Retrospective Claims Databse Analysis. in ASH 57th Annual Meeting & Exposition. 2015. Orlando, Florida.
24. Latagliata, R, D Ferrero, A Iurlo, F Cavazzini, F Castagnetti, E Abruzzese, C Fava, M Breccia, M Annunziata, F Stagno, M Tiribelli, G Binotto, G Mansueto, A Gozzini, S Russo, L Cavalli, E Montefusco, G Gugliotta, M Cedrone, A Russo Rossi, P Avanzini, P Pregno, E Mauro, A Spadea, F Celesti, G Giglio, A Isidori, M Crugnola, E Calistri, F Sora, S Storti, A D'Addosio, G Rege-Cambrin, L LucianoG Alimena, Imatinib in very elderly patients with chronic myeloid leukemia in chronic phase: a retrospective study. Drugs Aging. 2013;30(8):629–37.
25. Rosti, G, I Iacobucci, S Bassi, F Castagnetti, M Amabile, D Cilloni, A Poerio, S Soverini, F Palandri, G Rege Cambrin, F Iuliano, G Alimena, R Latagliata, N Testoni, F Pane, G Saglio, M BaccaraniG Martinelli, Impact of age on the outcome of patients with chronic myeloid leukemia in late chronic phase: results of a phase II study of the GIMEMA CML Working Party. Haematologica. 2007;92(1):101-5.
26. Hehlmann, R, MC Müller, M Lauseker, B Hanfstein, A Fabarius, A Schreiber, U Proetel, N Pletsch, M Pfirrmann, C Haferlach, S Schnittger, H Einsele, J Dengler, C Falge, L Kanz, A Neubauer, M Kneba, F Stegelmann, M Pfreundschuh, CF Waller, K Spiekermann, GM Baerlocher, G Ehninger, D Heim, H Heimpel, C Nerl, SW Krause, DK Hossfeld, HJ Kolb, J Hasford, S SausseleA Hochhaus, Deep molecular response is reached by the majority of patients treated with imatinib, predicts survival, and is achieved more quickly by optimized high-dose imatinib: results from the randomized CML-study IV. J Clin Oncol. 2014;32(5):415–23.
27. Kantarjian, H, NP Shah, A Hochhaus, J Cortes, S Shah, M Ayala, B Moiraghi, Z Shen, J Mayer, R Pasquini, H Nakamae, F Huguet, C Boque, C Chuah, E Bleickardt, MB Bradley-Garelik, C Zhu, T Szatrowski, D ShapiroM Baccarani, Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2010;362(24):2260–70.
28. O'Brien, SG, F Guilhot, RA Larson, I Gathmann, M Baccarani, F Cervantes, J Cornelissen, T Fischer, A Hochhaus, T Hughes, K Lechner, J Nielsen, P Rousselot, J Reiffers, G Saglio, J Shepherd, B Simonsson, A Gratwohl, J Goldman, H Kantarjian, K Taylor, G Verhoef, A Bolton, R Capdeville, B DrukerI Investigators., Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. The New England Journal of Medicine. 2003;348(11):994–1004.
29. Preudhomme, C, J Guilhot, FE Nicolini, A Guerci-Bresler, F Rigal-Huguet, F Maloisel, V Coiteux, M Gardembas, C Berthou, A Vekhoff, D Rea, E Jourdan, C Allard, A Delmer, P Rousselot, L Legros, M Berger, S Corm, G Etienne, C Roche-Lestienne, V Eclache, FX Mahon, F Guilhot, S InvestigatorsC France Intergroupe des Leucemies Myeloides, Imatinib plus peginterferon alfa-2a in chronic myeloid leukemia. N Engl J Med. 2010;363(26):2511–21.
30. Saglio, G, DW Kim, S Issaragrisil, P le Coutre, G Etienne, C Lobo, R Pasquini, RE Clark, A Hochhaus, TP Hughes, N Gallagher, A Hoenekopp, M Dong, A Haque, RA LarsonHM Kantarjian, Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010;362(24):2251–9.
31. Simonsson, B, T Gedde-Dahl, B Markevarn, K Remes, J Stentoft, A Almqvist, M Bjoreman, M Flogegard, P Koskenvesa, A Lindblom, C Malm, S Mustjoki, K Myhr-Eriksson, L Ohm, A Rasanen, M Sinisalo, A Sjalander, U Stromberg, OW Bjerrum, H Ehrencrona, F Gruber, V Kairisto, K Olsson, F Sandin, A Nagler, JL Nielsen, H Hjorth-Hansen, K PorkkaCMLSG Nordic, Combination of pegylated IFN-alpha2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia. Blood. 2011;118(12):3228–35.
32. Branford, S, L Fletcher, NC Cross, MC Muller, A Hochhaus, DW Kim, JP Radich, G Saglio, F Pane, S Kamel-Reid, YL Wang, RD Press, K Lynch, Z Rudzki, JM GoldmanT Hughes, Desirable performance characteristics for BCR-ABL measurement on an international reporting scale to allow consistent interpretation of individual patient response and comparison of response rates between clinical trials. Blood. 2008;112(8):3330-8.
33. Cross, NC, HE White, MC Müller, G SaglioA Hochhaus, Standardized definitions of molecular response in chronic myeloid leukemia. Leukemia. 2012;26(10):2172–5.
34. monitor, Thsap. Health systems in transition (HiT) profile of Italy. January 2018]; Available from: http://www.hspm.org/countries/italy25062012/livinghit.aspx?Section=5.6%20Pharmaceutical%20care&Type=Section.
35. Ferré, F, A Giulio de Belvis, L Valerio, S Longhi, A Lazzari, G Fattore, W RicciardiA Maresso. Italy Health system review. 2014 January 2018]; Available from: http://www.euro.who.int/__data/assets/pdf_file/0003/263253/HiT-Italy.pdf
36. Mauro, MJ, C Davis, T ZyczynskiHJ Khoury, The role of observational studies in optimizing the clinical management of chronic myeloid leukemia. Therapeutic Advances in Hematology. 2015;6(1):3–14.