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Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

The impact of introducing tyrosine kinase inhibitors on chronic myeloid leukemia survival: a population-based study

Authors: Enza Di Felice, Francesca Roncaglia, Francesco Venturelli, Lucia Mangone, Stefano Luminari, Claudia Cirilli, Giuliano Carrozzi, Paolo Giorgi Rossi

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

Chronic myeloid leukemia is associated with a BCR/ABL oncoprotein inhibited by imatinib mesylate, the first tyrosine kinase inhibitor. Although experimental studies have clearly demonstrated the efficacy of imatinib, up-to-date data on its effectiveness at the population level are limited.
Our study aims to assess the change in disease-specific survival for chronic myeloid leukemia after introducing tyrosine kinase inhibitors in first-line treatment.

Methods

This study analyzed data from two population-based cancer registries in Italy. Disease-specific survival for chronic myeloid leukemia cases diagnosed before and after the introduction of tyrosine kinase inhibitors (February 2002) were calculated up to 10 years. Hazard ratios were calculated using Cox regression models adjusted for sex, age at diagnosis and residency. An interrupted time series analysis was also performed.

Results

Between 1996 and 2012, 357 new cases of chronic myeloid leukemia were diagnosed (standardized incidence rate of 1.2 per 100,000 residents), quite constant throughout the period. The interrupted time series analysis showed a gain of 40.4% in 5 years of disease-specific survival for chronic myeloid leukemia (from 47.3, 95%CI 38.5–55.5% to 80.8%, 95%CI 74.5–85.8%) after the introduction of tyrosine kinase inhibitors. The hazard ratio was 0.36 (95%CI 0.25–0.52) for cases diagnosed after tyrosine kinase inhibitor introduction, with differences per age at diagnosis: <65yo 0.17 (95%CI 0.08–0.39), >74yo 0.41 (95%CI 0.23–0.73). An improvement in survival (hazard ratio 0.66, 95%CI 0.36–1.20) was also observed in cases diagnosed before, and alive at, tyrosine kinase inhibitors introduction.

Conclusions

Tyrosine kinase inhibitors increased disease-specific survival both for new and prevalent chronic myeloid leukemia cases. The effectiveness was similar to that observed in trials only in patients ages 65 years or younger.
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Literature
1.
go back to reference Cortes JE, Talpaz M, Kantarjian H. Chronic myelogenous leukemia: a review. Am J Med. 1996;100:555–70.CrossRef Cortes JE, Talpaz M, Kantarjian H. Chronic myelogenous leukemia: a review. Am J Med. 1996;100:555–70.CrossRef
2.
go back to reference Mariuzzi GM. In: PICCIN, editor. Anatomia Patologica e correlazioni anatomo-cliniche; 2006. Mariuzzi GM. In: PICCIN, editor. Anatomia Patologica e correlazioni anatomo-cliniche; 2006.
3.
go back to reference AIRTUM Working Group, Busco S, Buzzoni C, Mallone S, Trama A, Castaing M, et al. Italian cancer figures--report 2015: the burden of rare cancers in Italy. Epidemiol Prev. 2016;40:1–120. AIRTUM Working Group, Busco S, Buzzoni C, Mallone S, Trama A, Castaing M, et al. Italian cancer figures--report 2015: the burden of rare cancers in Italy. Epidemiol Prev. 2016;40:1–120.
4.
go back to reference Coviello V, Buzzoni C, Fusco M, AIRTUM Working Group. Italian cancer figures - report 2016. Survival of cancer patients in Italy. Epidemiol Prev. 2017;41. Coviello V, Buzzoni C, Fusco M, AIRTUM Working Group. Italian cancer figures - report 2016. Survival of cancer patients in Italy. Epidemiol Prev. 2017;41.
5.
go back to reference Sant M, Allemani C, Tereanu C, De Angelis R, Capocaccia R, Visser O, et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood. 2010;116:3724–34.CrossRef Sant M, Allemani C, Tereanu C, De Angelis R, Capocaccia R, Visser O, et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood. 2010;116:3724–34.CrossRef
7.
go back to reference Konopka JB, Watanabe SM, Witte ON. An alteration of the human c-abl protein in K562 leukemia cells unmasks associated tyrosine kinase activity. Cell. 1984;37:1035–42.CrossRef Konopka JB, Watanabe SM, Witte ON. An alteration of the human c-abl protein in K562 leukemia cells unmasks associated tyrosine kinase activity. Cell. 1984;37:1035–42.CrossRef
8.
go back to reference Buchdunger E, Zimmermann J, Mett H, Meyer T, Müller M, Druker BJ, et al. Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. Cancer Res. 1996;56:100–4.PubMed Buchdunger E, Zimmermann J, Mett H, Meyer T, Müller M, Druker BJ, et al. Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. Cancer Res. 1996;56:100–4.PubMed
9.
go back to reference O’Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, et al. Imatinib compared with interferon and low-dose Cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003;348:994–1004.CrossRef O’Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, et al. Imatinib compared with interferon and low-dose Cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003;348:994–1004.CrossRef
11.
go back to reference Simonsson B, Kloke O, Stahel RA. ESMO minimum clinical recommendations for the diagnosis, treatment and follow-up of chronic myelogenous leukemia (CML). Ann Oncol. 2005;16:i52–3.CrossRef Simonsson B, Kloke O, Stahel RA. ESMO minimum clinical recommendations for the diagnosis, treatment and follow-up of chronic myelogenous leukemia (CML). Ann Oncol. 2005;16:i52–3.CrossRef
12.
go back to reference Mughal TI, Radich JP, Deininger MW, Apperley JF, Hughes TP, Harrison CJ, et al. Chronic myeloid leukemia: reminiscences and dreams. Haematologica. 2016:541–58.CrossRef Mughal TI, Radich JP, Deininger MW, Apperley JF, Hughes TP, Harrison CJ, et al. Chronic myeloid leukemia: reminiscences and dreams. Haematologica. 2016:541–58.CrossRef
13.
go back to reference Banjar H, Ranasinghe D, Brown F, Adelson D, Kroger T, Leclercq T, et al. Modelling predictors of molecular response to frontline Imatinib for patients with chronic myeloid Leukaemia. PLoS One. 2017;12:e0168947.CrossRef Banjar H, Ranasinghe D, Brown F, Adelson D, Kroger T, Leclercq T, et al. Modelling predictors of molecular response to frontline Imatinib for patients with chronic myeloid Leukaemia. PLoS One. 2017;12:e0168947.CrossRef
14.
go back to reference O’Hare T, Eide CA, Deininger MWN. Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia. Blood. 2007:2242–9.CrossRef O’Hare T, Eide CA, Deininger MWN. Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia. Blood. 2007:2242–9.CrossRef
15.
go back to reference Baccarani M, Dreyling M. Chronic myeloid leukaemia: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21:v165–7.CrossRef Baccarani M, Dreyling M. Chronic myeloid leukaemia: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21:v165–7.CrossRef
16.
go back to reference Woywod C, Gruber FX, Engh RA, Flå T. Dynamical models of mutated chronic myelogenous leukemia cells for a postimatinib treatment scenario: response to dasatinib or nilotinib therapy. PLoS One. 2017;12:e0179700.CrossRef Woywod C, Gruber FX, Engh RA, Flå T. Dynamical models of mutated chronic myelogenous leukemia cells for a postimatinib treatment scenario: response to dasatinib or nilotinib therapy. PLoS One. 2017;12:e0179700.CrossRef
19.
go back to reference Kantarjian H, Giles F, Wunderle L, Bhalla K, O’Brien S, Wassmann B, et al. Nilotinib in Imatinib-resistant CML and Philadelphia chromosome–positive ALL. N Engl J Med. 2006;354:2542–51.CrossRef Kantarjian H, Giles F, Wunderle L, Bhalla K, O’Brien S, Wassmann B, et al. Nilotinib in Imatinib-resistant CML and Philadelphia chromosome–positive ALL. N Engl J Med. 2006;354:2542–51.CrossRef
20.
go back to reference Kantarjian H, Shah NP, Hochhaus A, Cortes J, Shah S, Ayala M, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2010;362:2260–70.CrossRef Kantarjian H, Shah NP, Hochhaus A, Cortes J, Shah S, Ayala M, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2010;362:2260–70.CrossRef
21.
go back to reference Saglio G, Kim D-W, Issaragrisil S, le Coutre P, Etienne G, Lobo C, et al. Nilotinib versus Imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010;362:2251–9.CrossRef Saglio G, Kim D-W, Issaragrisil S, le Coutre P, Etienne G, Lobo C, et al. Nilotinib versus Imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010;362:2251–9.CrossRef
22.
go back to reference Baccarani M, Pileri S, Steegmann J-L, Muller M, Soverini S, Dreyling M, et al. Chronic myeloid leukemia: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23:vii72–7.CrossRef Baccarani M, Pileri S, Steegmann J-L, Muller M, Soverini S, Dreyling M, et al. Chronic myeloid leukemia: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23:vii72–7.CrossRef
23.
go back to reference Druker BJ, Guilhot F, O’Brien SG, Gathmann I, Kantarjian H, Gattermann N, et al. Five-year follow-up of patients receiving Imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355:2408–17.CrossRef Druker BJ, Guilhot F, O’Brien SG, Gathmann I, Kantarjian H, Gattermann N, et al. Five-year follow-up of patients receiving Imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355:2408–17.CrossRef
24.
go back to reference Pulte D, Gondos A, Redaniel MT, Brenner H. Survival of patients with chronic myelocytic leukemia: comparisons of estimates from clinical trial settings and population-based cancer registries. Oncologist. 2011;16:663–71.CrossRef Pulte D, Gondos A, Redaniel MT, Brenner H. Survival of patients with chronic myelocytic leukemia: comparisons of estimates from clinical trial settings and population-based cancer registries. Oncologist. 2011;16:663–71.CrossRef
25.
go back to reference Björkholm M, Ohm L, Eloranta S, Derolf Å, Hultcrantz M, Sjöberg J, et al. Success story of targeted therapy in chronic myeloid leukemia: a population-based study of patients diagnosed in Sweden from 1973 to 2008. J Clin Oncol. 2011;29:2514–20.CrossRef Björkholm M, Ohm L, Eloranta S, Derolf Å, Hultcrantz M, Sjöberg J, et al. Success story of targeted therapy in chronic myeloid leukemia: a population-based study of patients diagnosed in Sweden from 1973 to 2008. J Clin Oncol. 2011;29:2514–20.CrossRef
26.
go back to reference Smith AG, Painter D, Howell DA, Evans P, Smith G, Patmore R, et al. Determinants of survival in patients with chronic myeloid leukaemia treated in the new era of oral therapy: findings from a UK population-based patient cohort. BMJ Open. 2014;4:e004266.CrossRef Smith AG, Painter D, Howell DA, Evans P, Smith G, Patmore R, et al. Determinants of survival in patients with chronic myeloid leukaemia treated in the new era of oral therapy: findings from a UK population-based patient cohort. BMJ Open. 2014;4:e004266.CrossRef
27.
go back to reference Pulte D, Barnes B, Jansen L, Eisemann N, Emrich K, Gondos A, et al. Population level survival of patients with chronic myelocytic leukemia in Germany compared to the US in the early 21st century. J Hematol Oncol. 2013;6:70.CrossRef Pulte D, Barnes B, Jansen L, Eisemann N, Emrich K, Gondos A, et al. Population level survival of patients with chronic myelocytic leukemia in Germany compared to the US in the early 21st century. J Hematol Oncol. 2013;6:70.CrossRef
28.
go back to reference Brunner AM, Campigotto F, Sadrzadeh H, Drapkin BJ, Chen Y-B, Neuberg DS, et al. Trends in all-cause mortality among patients with chronic myeloid leukemia. Cancer. 2013;119:2620–9.CrossRef Brunner AM, Campigotto F, Sadrzadeh H, Drapkin BJ, Chen Y-B, Neuberg DS, et al. Trends in all-cause mortality among patients with chronic myeloid leukemia. Cancer. 2013;119:2620–9.CrossRef
29.
go back to reference Chen Y, Wang H, Kantarjian H, Cortes J. Trends in chronic myeloid leukemia incidence and survival in the United States from 1975 to 2009. Leuk Lymphoma. 2013;54:1411–7.CrossRef Chen Y, Wang H, Kantarjian H, Cortes J. Trends in chronic myeloid leukemia incidence and survival in the United States from 1975 to 2009. Leuk Lymphoma. 2013;54:1411–7.CrossRef
30.
go back to reference Sant M, Minicozzi P, Mounier M, Anderson LA, Brenner H, Holleczek B, et al. Survival for haematological malignancies in Europe between 1997 and 2008 by region and age: results of EUROCARE-5, a population-based study. Lancet Oncol. 2014;15:931–42.CrossRef Sant M, Minicozzi P, Mounier M, Anderson LA, Brenner H, Holleczek B, et al. Survival for haematological malignancies in Europe between 1997 and 2008 by region and age: results of EUROCARE-5, a population-based study. Lancet Oncol. 2014;15:931–42.CrossRef
31.
go back to reference Beinortas T, Tavorienė I, Žvirblis T, Gerbutavičius R, Jurgutis M, Griškevičius L. Chronic myeloid leukemia incidence, survival and accessibility of tyrosine kinase inhibitors: a report from population-based Lithuanian haematological disease registry 2000–2013. BMC Cancer. 2016;16:198.CrossRef Beinortas T, Tavorienė I, Žvirblis T, Gerbutavičius R, Jurgutis M, Griškevičius L. Chronic myeloid leukemia incidence, survival and accessibility of tyrosine kinase inhibitors: a report from population-based Lithuanian haematological disease registry 2000–2013. BMC Cancer. 2016;16:198.CrossRef
32.
go back to reference Noens L, Hensen M, Kucmin-Bemelmans I, Lofgren C, Gilloteau I, Vrijens B. Measurement of adherence to BCR-ABL inhibitor therapy in chronic myeloid leukemia: current situation and future challenges. Haematologica. 2014:437–47.CrossRef Noens L, Hensen M, Kucmin-Bemelmans I, Lofgren C, Gilloteau I, Vrijens B. Measurement of adherence to BCR-ABL inhibitor therapy in chronic myeloid leukemia: current situation and future challenges. Haematologica. 2014:437–47.CrossRef
33.
go back to reference Kurtovic-Kozaric A, Hasic A, Radich JP, Bijedic V, Nefic H, Eminovic I, et al. The reality of cancer treatment in a developing country: the effects of delayed TKI treatment on survival, cytogenetic and molecular responses in chronic myeloid leukaemia patients. Br J Haematol. 2016;172:420–7.CrossRef Kurtovic-Kozaric A, Hasic A, Radich JP, Bijedic V, Nefic H, Eminovic I, et al. The reality of cancer treatment in a developing country: the effects of delayed TKI treatment on survival, cytogenetic and molecular responses in chronic myeloid leukaemia patients. Br J Haematol. 2016;172:420–7.CrossRef
34.
go back to reference Gallipoli P, Shepherd P, Irvine D, Drummond M, Holyoake T. Restricted access to second generation tyrosine kinase inhibitors in the UK could result in suboptimal treatment for almost half of chronic myeloid leukaemia patients: results from a west of Scotland and Lothian population study. Br J Haematol. 2011:128–30.CrossRef Gallipoli P, Shepherd P, Irvine D, Drummond M, Holyoake T. Restricted access to second generation tyrosine kinase inhibitors in the UK could result in suboptimal treatment for almost half of chronic myeloid leukaemia patients: results from a west of Scotland and Lothian population study. Br J Haematol. 2011:128–30.CrossRef
35.
go back to reference HAEMACARE Working Group. Manual for coding and reporting haematological malignancies. Tumori. 2010;96:i–A32. HAEMACARE Working Group. Manual for coding and reporting haematological malignancies. Tumori. 2010;96:i–A32.
37.
go back to reference Höglund M, Sandin F, Hellström K, Björeman M, Björkholm M, Brune M, et al. Tyrosine kinase inhibitor usage, treatment outcome, and prognostic scores in CML: report from the population-based Swedish CML registry. Blood. 2013;122:1284–92.CrossRef Höglund M, Sandin F, Hellström K, Björeman M, Björkholm M, Brune M, et al. Tyrosine kinase inhibitor usage, treatment outcome, and prognostic scores in CML: report from the population-based Swedish CML registry. Blood. 2013;122:1284–92.CrossRef
39.
go back to reference Bernal JL, Cummins S, Gasparrini A. Interrupted time series regression for the evaluation of public health interventions: a tutorial. Int J Epidemiol. 2017;46:348–55.PubMed Bernal JL, Cummins S, Gasparrini A. Interrupted time series regression for the evaluation of public health interventions: a tutorial. Int J Epidemiol. 2017;46:348–55.PubMed
40.
go back to reference Linden A. ITSA: Stata module to perform interrupted time series analysis for single and multiple groups. In: Stat. Softw. Components. Boston College Department of Economics; 2015. Linden A. ITSA: Stata module to perform interrupted time series analysis for single and multiple groups. In: Stat. Softw. Components. Boston College Department of Economics; 2015.
46.
go back to reference Castagnetti F, Di Raimondo F, De Vivo A, Spitaleri A, Gugliotta G, Fabbiano F, et al. A population-based study of chronic myeloid leukemia patients treated with imatinib in first line. Am J Hematol. 2017;92:82–7.CrossRef Castagnetti F, Di Raimondo F, De Vivo A, Spitaleri A, Gugliotta G, Fabbiano F, et al. A population-based study of chronic myeloid leukemia patients treated with imatinib in first line. Am J Hematol. 2017;92:82–7.CrossRef
Metadata
Title
The impact of introducing tyrosine kinase inhibitors on chronic myeloid leukemia survival: a population-based study
Authors
Enza Di Felice
Francesca Roncaglia
Francesco Venturelli
Lucia Mangone
Stefano Luminari
Claudia Cirilli
Giuliano Carrozzi
Paolo Giorgi Rossi
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4984-3

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