Skip to main content
Top
Published in: Annals of Hematology 5/2018

01-05-2018 | Review Article

Identification and assessment of frailty in older patients with chronic myeloid leukemia and myelofibrosis, and indications for tyrosine kinase inhibitor treatment

Authors: Massimo Breccia, Francesca Palandri, Luigiana Luciano, Giulia Benevolo, Massimiliano Bonifacio, Giovanni Caocci, Fausto Castagnetti, Giuseppe A. Palumbo, Alessandra Iurlo, Francesco Landi

Published in: Annals of Hematology | Issue 5/2018

Login to get access

Abstract

The incidence of cancer, including myeloproliferative neoplasms (MPNs), is projected to increase significantly due to the growing proportion of people aged > 65 years. These older individuals are a heterogeneous population in terms of fitness, comorbidity, and psychological reserve. Therefore, age per se does not always provide an accurate indication of condition in patients with cancer. Frailty has been proposed as an alternative measure of vulnerability that might better indicate which patients can tolerate standard cancer treatment and those who may benefit from treatment adjustment. A number of methods can be used to assess frailty in older patients with hematological malignancies, including the Cardiovascular Health Study Frailty Screening Measure, the FRAIL (Fatigue, Resistance, Ambulation, Illnesses, and Loss of weight) questionnaire, the Clinical Frailty Scale (CFS), and the Gérontopôle Frailty Screening Tool. In addition to physical frailty, comorbidity and quality of life should also be included in the assessment. Prior to the introduction of tyrosine kinase inhibitors (TKIs), age was considered a marker of poor prognosis in patients with MPNs. In contrast, data show that age is not necessarily a contraindication for TKI use. In CML, the efficacy of TKIs has been shown to be independent of age. The JAK1/2 inhibitor ruxolitinib also seems to be effective across a range of patient ages. Available data suggest that chronological age itself should not necessarily be a contraindication for many new therapies in patients with MPNs, and that frailty does provide a better measure of vulnerability. There is a need for specific methods to assess frailty in patients with MPNs, particularly the context of effective new treatment options, such as TKIs and ruxolitinib.
Literature
8.
go back to reference Corre R, Greillier L, Le Caer H, Audigier-Valette C, Baize N, Berard H, Falchero L, Monnet I, Dansin E, Vergnenegre A, Marcq M, Decroisette C, Auliac JB, Bota S, Lamy R, Massuti B, Dujon C, Perol M, Daures JP, Descourt R, Lena H, Plassot C, Chouaid C (2016) Use of a comprehensive geriatric assessment for the management of elderly patients with advanced non-small-cell lung cancer: the Phase III Randomized ESOGIA-GFPC-GECP 08-02 Study. J Clin Oncol 34(13):1476–1483. https://doi.org/10.1200/JCO.2015.63.5839 PubMedCrossRef Corre R, Greillier L, Le Caer H, Audigier-Valette C, Baize N, Berard H, Falchero L, Monnet I, Dansin E, Vergnenegre A, Marcq M, Decroisette C, Auliac JB, Bota S, Lamy R, Massuti B, Dujon C, Perol M, Daures JP, Descourt R, Lena H, Plassot C, Chouaid C (2016) Use of a comprehensive geriatric assessment for the management of elderly patients with advanced non-small-cell lung cancer: the Phase III Randomized ESOGIA-GFPC-GECP 08-02 Study. J Clin Oncol 34(13):1476–1483. https://​doi.​org/​10.​1200/​JCO.​2015.​63.​5839 PubMedCrossRef
11.
go back to reference European Medicines Agency (2009) Glivec: EPAR—product information. European Medicines Agency, London European Medicines Agency (2009) Glivec: EPAR—product information. European Medicines Agency, London
12.
go back to reference European Medicines Agency (2012) Jakavi: EPAR—product information. European Medicines Agency, London European Medicines Agency (2012) Jakavi: EPAR—product information. European Medicines Agency, London
17.
19.
23.
go back to reference Marzetti E, Calvani R, Cesari M, Tosato M, Cherubini A, Di Bari M, Pahor M, Savera G, Collamati A, D'Angelo E, Bernabei R, Landi F (2015) Operationalization of the physical frailty & sarcopenia syndrome: rationale and clinical implementation. Transl Med UniSa 13:29–32PubMed Marzetti E, Calvani R, Cesari M, Tosato M, Cherubini A, Di Bari M, Pahor M, Savera G, Collamati A, D'Angelo E, Bernabei R, Landi F (2015) Operationalization of the physical frailty & sarcopenia syndrome: rationale and clinical implementation. Transl Med UniSa 13:29–32PubMed
28.
go back to reference Palumbo A, Bringhen S, Mateos MV, Larocca A, Facon T, Kumar SK, Offidani M, McCarthy P, Evangelista A, Lonial S, Zweegman S, Musto P, Terpos E, Belch A, Hajek R, Ludwig H, Stewart AK, Moreau P, Anderson K, Einsele H, Durie BG, Dimopoulos MA, Landgren O, San Miguel JF, Richardson P, Sonneveld P, Rajkumar SV (2015) Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood 125(13):2068–2074. https://doi.org/10.1182/blood-2014-12-615187 PubMedCrossRefPubMedCentral Palumbo A, Bringhen S, Mateos MV, Larocca A, Facon T, Kumar SK, Offidani M, McCarthy P, Evangelista A, Lonial S, Zweegman S, Musto P, Terpos E, Belch A, Hajek R, Ludwig H, Stewart AK, Moreau P, Anderson K, Einsele H, Durie BG, Dimopoulos MA, Landgren O, San Miguel JF, Richardson P, Sonneveld P, Rajkumar SV (2015) Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood 125(13):2068–2074. https://​doi.​org/​10.​1182/​blood-2014-12-615187 PubMedCrossRefPubMedCentral
29.
go back to reference Buckstein R, Wells RA, Zhu N, Leitch HA, Nevill TJ, Yee KW, Leber B, Sabloff M, St Hilaire E, Kumar R, Geddes M, Shamy A, Storring J, Kew A, Elemary M, Levitt M, Lenis M, Mamedov A, Zhang L, Rockwood K, Alibhai SM (2016) Patient-related factors independently impact overall survival in patients with myelodysplastic syndromes: an MDS-CAN prospective study. Br J Haematol 174(1):88–101. https://doi.org/10.1111/bjh.14033 PubMedCrossRef Buckstein R, Wells RA, Zhu N, Leitch HA, Nevill TJ, Yee KW, Leber B, Sabloff M, St Hilaire E, Kumar R, Geddes M, Shamy A, Storring J, Kew A, Elemary M, Levitt M, Lenis M, Mamedov A, Zhang L, Rockwood K, Alibhai SM (2016) Patient-related factors independently impact overall survival in patients with myelodysplastic syndromes: an MDS-CAN prospective study. Br J Haematol 174(1):88–101. https://​doi.​org/​10.​1111/​bjh.​14033 PubMedCrossRef
31.
go back to reference Rodriguez-Manas L, Feart C, Mann G, Vina J, Chatterji S, Chodzko-Zajko W, Gonzalez-Colaco Harmand M, Bergman H, Carcaillon L, Nicholson C, Scuteri A, Sinclair A, Pelaez M, Van der Cammen T, Beland F, Bickenbach J, Delamarche P, Ferrucci L, Fried LP, Gutierrez-Robledo LM, Rockwood K, Rodriguez Artalejo F, Serviddio G, Vega E, Fod-Cc group (2013) Searching for an operational definition of frailty: a Delphi method based consensus statement: the frailty operative definition-consensus conference project. J Gerontol A Biol Sci Med Sci 68(1):62–67. https://doi.org/10.1093/gerona/gls119 PubMedCrossRef Rodriguez-Manas L, Feart C, Mann G, Vina J, Chatterji S, Chodzko-Zajko W, Gonzalez-Colaco Harmand M, Bergman H, Carcaillon L, Nicholson C, Scuteri A, Sinclair A, Pelaez M, Van der Cammen T, Beland F, Bickenbach J, Delamarche P, Ferrucci L, Fried LP, Gutierrez-Robledo LM, Rockwood K, Rodriguez Artalejo F, Serviddio G, Vega E, Fod-Cc group (2013) Searching for an operational definition of frailty: a Delphi method based consensus statement: the frailty operative definition-consensus conference project. J Gerontol A Biol Sci Med Sci 68(1):62–67. https://​doi.​org/​10.​1093/​gerona/​gls119 PubMedCrossRef
40.
go back to reference Abellan van Kan G, Rolland Y, Andrieu S, Bauer J, Beauchet O, Bonnefoy M, Cesari M, Donini LM, Gillette Guyonnet S, Inzitari M, Nourhashemi F, Onder G, Ritz P, Salva A, Visser M, Vellas B (2009) Gait speed at usual pace as a predictor of adverse outcomes in community-dwelling older people an International Academy on Nutrition and Aging (IANA) Task Force. J Nutr Health Aging 13(10):881–889. https://doi.org/10.1007/s12603-009-0246-z PubMedCrossRef Abellan van Kan G, Rolland Y, Andrieu S, Bauer J, Beauchet O, Bonnefoy M, Cesari M, Donini LM, Gillette Guyonnet S, Inzitari M, Nourhashemi F, Onder G, Ritz P, Salva A, Visser M, Vellas B (2009) Gait speed at usual pace as a predictor of adverse outcomes in community-dwelling older people an International Academy on Nutrition and Aging (IANA) Task Force. J Nutr Health Aging 13(10):881–889. https://​doi.​org/​10.​1007/​s12603-009-0246-z PubMedCrossRef
42.
go back to reference Hubbard RE, Lang IA, Llewellyn DJ, Rockwood K (2010) Frailty, body mass index, and abdominal obesity in older people. J Gerontol A Biol Sci Med Sci 65:377–381PubMedCrossRef Hubbard RE, Lang IA, Llewellyn DJ, Rockwood K (2010) Frailty, body mass index, and abdominal obesity in older people. J Gerontol A Biol Sci Med Sci 65:377–381PubMedCrossRef
43.
go back to reference Guralnik JM, Ferrucci L, Pieper CF, Leveille SG, Markides KS, Ostir GV, Studenski S, Berkman LF, Wallace RB (2000) Lower extremity function and subsequent disability: consistency across studies, predictive models, and value of gait speed alone compared with the short physical performance battery. J Gerontol A Biol Sci Med Sci 55(4):M221–M231. https://doi.org/10.1093/gerona/55.4.M221 PubMedCrossRef Guralnik JM, Ferrucci L, Pieper CF, Leveille SG, Markides KS, Ostir GV, Studenski S, Berkman LF, Wallace RB (2000) Lower extremity function and subsequent disability: consistency across studies, predictive models, and value of gait speed alone compared with the short physical performance battery. J Gerontol A Biol Sci Med Sci 55(4):M221–M231. https://​doi.​org/​10.​1093/​gerona/​55.​4.​M221 PubMedCrossRef
44.
go back to reference Landi F, Cesari M, Calvani R, Cherubini A, Di Bari M, Bejuit R, Mshid J, Andrieu S, Sinclair AJ, Sieber CC, Vellas B, Topinkova E, Strandberg T, Rodriguez-Manas L, Lattanzio F, Pahor M, Roubenoff R, Cruz-Jentoft AJ, Bernabei R, Marzetti E, Consortium S (2017) The "Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies" (SPRINTT) randomized controlled trial: design and methods. Aging Clin Exp Res 29(1):89–100. https://doi.org/10.1007/s40520-016-0715-2 PubMedCrossRef Landi F, Cesari M, Calvani R, Cherubini A, Di Bari M, Bejuit R, Mshid J, Andrieu S, Sinclair AJ, Sieber CC, Vellas B, Topinkova E, Strandberg T, Rodriguez-Manas L, Lattanzio F, Pahor M, Roubenoff R, Cruz-Jentoft AJ, Bernabei R, Marzetti E, Consortium S (2017) The "Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies" (SPRINTT) randomized controlled trial: design and methods. Aging Clin Exp Res 29(1):89–100. https://​doi.​org/​10.​1007/​s40520-016-0715-2 PubMedCrossRef
47.
go back to reference Cortes J, Talpaz M, O'Brien S, Giles F, Beth Rios M, Shan J, Faderl S, Garcia-Manero G, Ferrajoli A, Wierda W, Kantarjian H (2003) Effects of age on prognosis with imatinib mesylate therapy for patients with Philadelphia chromosome-positive chronic myelogenous leukemia. Cancer 98(6):1105–1113. https://doi.org/10.1002/cncr.11629 PubMedCrossRef Cortes J, Talpaz M, O'Brien S, Giles F, Beth Rios M, Shan J, Faderl S, Garcia-Manero G, Ferrajoli A, Wierda W, Kantarjian H (2003) Effects of age on prognosis with imatinib mesylate therapy for patients with Philadelphia chromosome-positive chronic myelogenous leukemia. Cancer 98(6):1105–1113. https://​doi.​org/​10.​1002/​cncr.​11629 PubMedCrossRef
48.
go back to reference Latagliata R, Breccia M, Carmosino I, Sarlo C, Montefusco E, Mancini M, Chistolini A, De Cuia R, Russo E, Salvatore GM, Biondo F, Spadea A, Mandelli F, Alimena G, Natalino F (2005) Elderly patients with Ph+ chronic myelogenous leukemia (CML): results of imatinib mesylate treatment. Leukemia Res 29:287–291CrossRef Latagliata R, Breccia M, Carmosino I, Sarlo C, Montefusco E, Mancini M, Chistolini A, De Cuia R, Russo E, Salvatore GM, Biondo F, Spadea A, Mandelli F, Alimena G, Natalino F (2005) Elderly patients with Ph+ chronic myelogenous leukemia (CML): results of imatinib mesylate treatment. Leukemia Res 29:287–291CrossRef
49.
go back to reference Rosti G, Iacobucci I, Bassi S, Castagnetti F, Amabile M, Cilloni D, Poerio A, Soverini S, Palandri F, Rege Cambrin G, Iuliano F, Alimena G, Latagliata R, Testoni N, Pane F, Saglio G, Baccarani M, Martinelli G (2007) 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 92(1):101–105. https://doi.org/10.3324/haematol.10239 PubMedCrossRef Rosti G, Iacobucci I, Bassi S, Castagnetti F, Amabile M, Cilloni D, Poerio A, Soverini S, Palandri F, Rege Cambrin G, Iuliano F, Alimena G, Latagliata R, Testoni N, Pane F, Saglio G, Baccarani M, Martinelli G (2007) 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 92(1):101–105. https://​doi.​org/​10.​3324/​haematol.​10239 PubMedCrossRef
50.
go back to reference Castagnetti F, Gugliotta G, Baccarani M, Breccia M, Specchia G, Levato L, Abruzzese E, Rossi G, Iurlo A, Martino B, Pregno P, Stagno F, Cuneo A, Bonifacio M, Gobbi M, Russo D, Gozzini A, Tiribelli M, de Vivo A, Alimena G, Cavo M, Martinelli G, Pane F, Saglio G, Rosti G (2015) Differences among young adults, adults and elderly chronic myeloid leukemia patients. Annals of oncology : official journal of the European Society for Medical Oncology 26(1):185–192. https://doi.org/10.1093/annonc/mdu490 CrossRef Castagnetti F, Gugliotta G, Baccarani M, Breccia M, Specchia G, Levato L, Abruzzese E, Rossi G, Iurlo A, Martino B, Pregno P, Stagno F, Cuneo A, Bonifacio M, Gobbi M, Russo D, Gozzini A, Tiribelli M, de Vivo A, Alimena G, Cavo M, Martinelli G, Pane F, Saglio G, Rosti G (2015) Differences among young adults, adults and elderly chronic myeloid leukemia patients. Annals of oncology : official journal of the European Society for Medical Oncology 26(1):185–192. https://​doi.​org/​10.​1093/​annonc/​mdu490 CrossRef
51.
go back to reference Saussele S, Krauss MP, Hehlmann R, Lauseker M, Proetel U, Kalmanti L, Hanfstein B, Fabarius A, Kraemer D, Berdel WE, Bentz M, Staib P, de Wit M, Wernli M, Zettl F, Hebart HF, Hahn M, Heymanns J, Schmidt-Wolf I, Schmitz N, Eckart MJ, Gassmann W, Bartholomaus A, Pezzutto A, Leibundgut EO, Heim D, Krause SW, Burchert A, Hofmann WK, Hasford J, Hochhaus A, Pfirrmann M, Muller MC (2015) Impact of comorbidities on overall survival in patients with chronic myeloid leukemia: results of the randomized CML study IV. Blood 126(1):42–49. https://doi.org/10.1182/blood-2015-01-617993 PubMedCrossRefPubMedCentral Saussele S, Krauss MP, Hehlmann R, Lauseker M, Proetel U, Kalmanti L, Hanfstein B, Fabarius A, Kraemer D, Berdel WE, Bentz M, Staib P, de Wit M, Wernli M, Zettl F, Hebart HF, Hahn M, Heymanns J, Schmidt-Wolf I, Schmitz N, Eckart MJ, Gassmann W, Bartholomaus A, Pezzutto A, Leibundgut EO, Heim D, Krause SW, Burchert A, Hofmann WK, Hasford J, Hochhaus A, Pfirrmann M, Muller MC (2015) Impact of comorbidities on overall survival in patients with chronic myeloid leukemia: results of the randomized CML study IV. Blood 126(1):42–49. https://​doi.​org/​10.​1182/​blood-2015-01-617993 PubMedCrossRefPubMedCentral
52.
go back to reference Iurlo A, Nobili A, Latagliata R, Bucelli C, Castagnetti F, Breccia M, Abruzzese E, Cattaneo D, Fava C, Ferrero D, Gozzini A, Bonifacio M, Tiribelli M, Pregno P, Stagno F, Vigneri P, Annunziata M, Cavazzini F, Binotto G, Mansueto G, Russo S, Falzetti F, Montefusco E, Gugliotta G, Storti S, D'Addosio AM, Scaffidi L, Cortesi L, Cedrone M, Rossi AR, Avanzini P, Mauro E, Spadea A, Celesti F, Giglio G, Isidori A, Crugnola M, Calistri E, Sora F, Rege-Cambrin G, Sica S, Luciano L, Galimberti S, Orlandi EM, Bocchia M, Tettamanti M, Alimena G, Saglio G, Rosti G, Mannucci PM, Cortelezzi A (2016) Imatinib and polypharmacy in very old patients with chronic myeloid leukemia: effects on response rate, toxicity and outcome. Oncotarget 7(48):80083–80090. https://doi.org/10.18632/oncotarget.11657 PubMedCrossRefPubMedCentral Iurlo A, Nobili A, Latagliata R, Bucelli C, Castagnetti F, Breccia M, Abruzzese E, Cattaneo D, Fava C, Ferrero D, Gozzini A, Bonifacio M, Tiribelli M, Pregno P, Stagno F, Vigneri P, Annunziata M, Cavazzini F, Binotto G, Mansueto G, Russo S, Falzetti F, Montefusco E, Gugliotta G, Storti S, D'Addosio AM, Scaffidi L, Cortesi L, Cedrone M, Rossi AR, Avanzini P, Mauro E, Spadea A, Celesti F, Giglio G, Isidori A, Crugnola M, Calistri E, Sora F, Rege-Cambrin G, Sica S, Luciano L, Galimberti S, Orlandi EM, Bocchia M, Tettamanti M, Alimena G, Saglio G, Rosti G, Mannucci PM, Cortelezzi A (2016) Imatinib and polypharmacy in very old patients with chronic myeloid leukemia: effects on response rate, toxicity and outcome. Oncotarget 7(48):80083–80090. https://​doi.​org/​10.​18632/​oncotarget.​11657 PubMedCrossRefPubMedCentral
53.
go back to reference Falchi L, Kantarjian HM, Wang X, Verma D, Quintas-Cardama A, O’Brien S, Jabbour EJ, Ravandi-Kashani F, Borthakur G, Garcia-Manero G, Verstovsek S, Burger JA, Luthra R, Cortes JE (2013) Significance of deeper molecular responses in patients with chronic myeloid leukemia in early chronic phase treated with tyrosine kinase inhibitors. Am J Hematol 88(12):1024–1029. https://doi.org/10.1002/ajh.23560 PubMedCrossRef Falchi L, Kantarjian HM, Wang X, Verma D, Quintas-Cardama A, O’Brien S, Jabbour EJ, Ravandi-Kashani F, Borthakur G, Garcia-Manero G, Verstovsek S, Burger JA, Luthra R, Cortes JE (2013) Significance of deeper molecular responses in patients with chronic myeloid leukemia in early chronic phase treated with tyrosine kinase inhibitors. Am J Hematol 88(12):1024–1029. https://​doi.​org/​10.​1002/​ajh.​23560 PubMedCrossRef
54.
go back to reference Hochhaus A, Rosti G, Cross NC, Steegmann JL, le Coutre P, Ossenkoppele G, Petrov L, Masszi T, Hellmann A, Griskevicius L, Wiktor-Jedrzejczak W, Rea D, Coriu D, Brummendorf TH, Porkka K, Saglio G, Gastl G, Muller MC, Schuld P, Di Matteo P, Pellegrino A, Dezzani L, Mahon FX, Baccarani M, Giles FJ (2016) Frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the European ENEST1st study. Leukemia 30(1):57–64. https://doi.org/10.1038/leu.2015.270 PubMedCrossRef Hochhaus A, Rosti G, Cross NC, Steegmann JL, le Coutre P, Ossenkoppele G, Petrov L, Masszi T, Hellmann A, Griskevicius L, Wiktor-Jedrzejczak W, Rea D, Coriu D, Brummendorf TH, Porkka K, Saglio G, Gastl G, Muller MC, Schuld P, Di Matteo P, Pellegrino A, Dezzani L, Mahon FX, Baccarani M, Giles FJ (2016) Frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the European ENEST1st study. Leukemia 30(1):57–64. https://​doi.​org/​10.​1038/​leu.​2015.​270 PubMedCrossRef
55.
go back to reference Hochhaus A, Saglio G, Hughes TP, Larson RA, Kim DW, Issaragrisil S, le Coutre PD, Etienne G, Dorlhiac-Llacer PE, Clark RE, Flinn IW, Nakamae H, Donohue B, Deng W, Dalal D, Menssen HD, Kantarjian HM (2016) 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 30(5):1044–1054. https://doi.org/10.1038/leu.2016.5 PubMedCrossRefPubMedCentral Hochhaus A, Saglio G, Hughes TP, Larson RA, Kim DW, Issaragrisil S, le Coutre PD, Etienne G, Dorlhiac-Llacer PE, Clark RE, Flinn IW, Nakamae H, Donohue B, Deng W, Dalal D, Menssen HD, Kantarjian HM (2016) 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 30(5):1044–1054. https://​doi.​org/​10.​1038/​leu.​2016.​5 PubMedCrossRefPubMedCentral
56.
go back to reference Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, Pasquini R, Clark RE, Hochhaus A, Hughes TP, Gallagher N, Hoenekopp A, Dong M, Haque A, Larson RA, Kantarjian HM (2010) Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 362(24):2251–2259. https://doi.org/10.1056/NEJMoa0912614 PubMedCrossRef Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, Pasquini R, Clark RE, Hochhaus A, Hughes TP, Gallagher N, Hoenekopp A, Dong M, Haque A, Larson RA, Kantarjian HM (2010) Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 362(24):2251–2259. https://​doi.​org/​10.​1056/​NEJMoa0912614 PubMedCrossRef
57.
go back to reference Hochhaus A, Masszi T, Giles FJ, Radich JP, Ross DM, Gomez Casares MT, Hellmann A, Stentoft J, Conneally E, Garcia-Gutierrez V, Gattermann N, Wiktor-Jedrzejczak W, le Coutre PD, Martino B, Saussele S, Menssen HD, Deng W, Krunic N, Bedoucha V, Saglio G (2017) Treatment-free remission following frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the ENEST freedom study. Leukemia 31(7):1525–1531. https://doi.org/10.1038/leu.2017.63 PubMedCrossRefPubMedCentral Hochhaus A, Masszi T, Giles FJ, Radich JP, Ross DM, Gomez Casares MT, Hellmann A, Stentoft J, Conneally E, Garcia-Gutierrez V, Gattermann N, Wiktor-Jedrzejczak W, le Coutre PD, Martino B, Saussele S, Menssen HD, Deng W, Krunic N, Bedoucha V, Saglio G (2017) Treatment-free remission following frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the ENEST freedom study. Leukemia 31(7):1525–1531. https://​doi.​org/​10.​1038/​leu.​2017.​63 PubMedCrossRefPubMedCentral
58.
go back to reference Ross D, Masszi T, Gomez Casares MT, Hellmann A, Stentoft J, Conneally E, Garcia-Gutierrez V, Gattermann N, le Coutre P, Martino B, Saussele S, Giles F, Radich J, Saglio G, Gopalakrishna P, Deng W, Krunic N, Bedoucha V, Hochhaus A (2017) Durable treatment-free remission (TFR) following frontline nilotinib (NIL) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP): ENESTFREESOM 96-WK update. Paper presented at the European Hematology Association Congress, Madrid, Spain, 22–25 June Ross D, Masszi T, Gomez Casares MT, Hellmann A, Stentoft J, Conneally E, Garcia-Gutierrez V, Gattermann N, le Coutre P, Martino B, Saussele S, Giles F, Radich J, Saglio G, Gopalakrishna P, Deng W, Krunic N, Bedoucha V, Hochhaus A (2017) Durable treatment-free remission (TFR) following frontline nilotinib (NIL) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP): ENESTFREESOM 96-WK update. Paper presented at the European Hematology Association Congress, Madrid, Spain, 22–25 June
59.
go back to reference Cervantes F, Dupriez B, Pereira A, Passamonti F, Reilly JT, Morra E, Vannucchi AM, Mesa RA, Demory JL, Barosi G, Rumi E, Tefferi A (2009) New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood 113(13):2895–2901. https://doi.org/10.1182/blood-2008-07-170449 PubMedCrossRef Cervantes F, Dupriez B, Pereira A, Passamonti F, Reilly JT, Morra E, Vannucchi AM, Mesa RA, Demory JL, Barosi G, Rumi E, Tefferi A (2009) New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood 113(13):2895–2901. https://​doi.​org/​10.​1182/​blood-2008-07-170449 PubMedCrossRef
60.
go back to reference Gangat N, Caramazza D, Vaidya R, George G, Begna K, Schwager S, Van Dyke D, Hanson C, Wu W, Pardanani A, Cervantes F, Passamonti F, Tefferi A (2011) DIPSS plus: a refined Dynamic International Prognostic Scoring System for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol 29(4):392–397. https://doi.org/10.1200/JCO.2010.32.2446 PubMedCrossRef Gangat N, Caramazza D, Vaidya R, George G, Begna K, Schwager S, Van Dyke D, Hanson C, Wu W, Pardanani A, Cervantes F, Passamonti F, Tefferi A (2011) DIPSS plus: a refined Dynamic International Prognostic Scoring System for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol 29(4):392–397. https://​doi.​org/​10.​1200/​JCO.​2010.​32.​2446 PubMedCrossRef
61.
go back to reference Passamonti F, Cervantes F, Vannucchi AM, Morra E, Rumi E, Pereira A, Guglielmelli P, Pungolino E, Caramella M, Maffioli M, Pascutto C, Lazzarino M, Cazzola M, Tefferi A (2010) A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment). Blood 115(9):1703–1708. https://doi.org/10.1182/blood-2009-09-245837 PubMedCrossRef Passamonti F, Cervantes F, Vannucchi AM, Morra E, Rumi E, Pereira A, Guglielmelli P, Pungolino E, Caramella M, Maffioli M, Pascutto C, Lazzarino M, Cazzola M, Tefferi A (2010) A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment). Blood 115(9):1703–1708. https://​doi.​org/​10.​1182/​blood-2009-09-245837 PubMedCrossRef
62.
go back to reference Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V, McQuitty M, Hunter DS, Levy R, Knoops L, Cervantes F, Vannucchi AM, Barbui T, Barosi G (2012) JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 366(9):787–798. https://doi.org/10.1056/NEJMoa1110556 PubMedCrossRef Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V, McQuitty M, Hunter DS, Levy R, Knoops L, Cervantes F, Vannucchi AM, Barbui T, Barosi G (2012) JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 366(9):787–798. https://​doi.​org/​10.​1056/​NEJMoa1110556 PubMedCrossRef
63.
go back to reference Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, Catalano JV, Deininger M, Miller C, Silver RT, Talpaz M, Winton EF, Harvey JH Jr, Arcasoy MO, Hexner E, Lyons RM, Paquette R, Raza A, Vaddi K, Erickson-Viitanen S, Koumenis IL, Sun W, Sandor V, Kantarjian HM (2012) A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med 366(9):799–807. https://doi.org/10.1056/NEJMoa1110557 PubMedCrossRefPubMedCentral Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, Catalano JV, Deininger M, Miller C, Silver RT, Talpaz M, Winton EF, Harvey JH Jr, Arcasoy MO, Hexner E, Lyons RM, Paquette R, Raza A, Vaddi K, Erickson-Viitanen S, Koumenis IL, Sun W, Sandor V, Kantarjian HM (2012) A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med 366(9):799–807. https://​doi.​org/​10.​1056/​NEJMoa1110557 PubMedCrossRefPubMedCentral
64.
go back to reference Foltz L, Palumbo A, Martino B, Palandri F, Al-Ali HK, Liberati AM, le Coutre P, Vannucchi AM, Garcia-Hernandez C, Tavares R, Griesshammer M, Gupta V, Raanani P, Giraldo P, Bouard C, Roncho JP, Khanna S, Zaritskey A (2016) Safety and efficacy of ruxolitinib for the final enrollment of JUMP: an open-label, multicenter, single-arm, expanded-access study in patients with myelofibrosis (n=2233). Blood 128:3107 Foltz L, Palumbo A, Martino B, Palandri F, Al-Ali HK, Liberati AM, le Coutre P, Vannucchi AM, Garcia-Hernandez C, Tavares R, Griesshammer M, Gupta V, Raanani P, Giraldo P, Bouard C, Roncho JP, Khanna S, Zaritskey A (2016) Safety and efficacy of ruxolitinib for the final enrollment of JUMP: an open-label, multicenter, single-arm, expanded-access study in patients with myelofibrosis (n=2233). Blood 128:3107
65.
go back to reference Cervantes F, Vannucchi AM, Kiladjian JJ, Al-Ali HK, Sirulnik A, Stalbovskaya V, McQuitty M, Hunter DS, Levy RS, Passamonti F, Barbui T, Barosi G, Harrison CN, Knoops L, Gisslinger H, investigators C-I (2013) Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Blood 122(25):4047–4053. https://doi.org/10.1182/blood-2013-02-485888 PubMedCrossRef Cervantes F, Vannucchi AM, Kiladjian JJ, Al-Ali HK, Sirulnik A, Stalbovskaya V, McQuitty M, Hunter DS, Levy RS, Passamonti F, Barbui T, Barosi G, Harrison CN, Knoops L, Gisslinger H, investigators C-I (2013) Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Blood 122(25):4047–4053. https://​doi.​org/​10.​1182/​blood-2013-02-485888 PubMedCrossRef
66.
go back to reference Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, Catalano JV, Deininger M, Miller C, Silver RT, Talpaz M, Winton EF, Harvey JH Jr, Arcasoy MO, Hexner E, Lyons RM, Paquette R, Raza A, Vaddi K, Erickson-Viitanen S, Sun W, Sandor V, Kantarjian HM (2013) The clinical benefit of ruxolitinib across patient subgroups: analysis of a placebo-controlled, Phase III study in patients with myelofibrosis. Br J Haematol 161(4):508–516. https://doi.org/10.1111/bjh.12274 PubMedCrossRefPubMedCentral Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, Catalano JV, Deininger M, Miller C, Silver RT, Talpaz M, Winton EF, Harvey JH Jr, Arcasoy MO, Hexner E, Lyons RM, Paquette R, Raza A, Vaddi K, Erickson-Viitanen S, Sun W, Sandor V, Kantarjian HM (2013) The clinical benefit of ruxolitinib across patient subgroups: analysis of a placebo-controlled, Phase III study in patients with myelofibrosis. Br J Haematol 161(4):508–516. https://​doi.​org/​10.​1111/​bjh.​12274 PubMedCrossRefPubMedCentral
67.
go back to reference Latagliata R, Di Veroli A, Palumbo GA, Bonifacio M, Andriani A, Polverelli N, Trawinska M, Tiribelli M, Anaclerico B, Benevolo G, Petriccione L, Martino B, Centra A, D’Adda M, Crugnola M, Cavazzini F, Bergamaschi M, Tieghi A, Ibatici A, Bosi C, Perricone M, Montanaro M, Cavo M, Breccia M, Vianelli N, Palandri F (2016) Efficacy and safety of ruxolitinib in elderly patients (> 75 years) with myelofibrosis. Paper presented at the American Society of Hematology 58th Annual Meeting & Exposition, San Diego, California Latagliata R, Di Veroli A, Palumbo GA, Bonifacio M, Andriani A, Polverelli N, Trawinska M, Tiribelli M, Anaclerico B, Benevolo G, Petriccione L, Martino B, Centra A, D’Adda M, Crugnola M, Cavazzini F, Bergamaschi M, Tieghi A, Ibatici A, Bosi C, Perricone M, Montanaro M, Cavo M, Breccia M, Vianelli N, Palandri F (2016) Efficacy and safety of ruxolitinib in elderly patients (> 75 years) with myelofibrosis. Paper presented at the American Society of Hematology 58th Annual Meeting & Exposition, San Diego, California
68.
go back to reference Raanani P, Gupta V, Sadjadian P, Al-Ali HK, Giraldo P, Guglielmelli P, Foltz L, Tavares R, Zaritskey A, Bouard C, Roncho JP, Tiwari R, Martino B (2017) Safety and efficacy of ruxolitinib (RUX) in elderly patients (≥ 75 years) with myelofibrosis (MF): an analysis from the phase 3b, expanded access JUMP study paper presented at the European Hematology Association Congress, Madrid, Spain, 22–25 June Raanani P, Gupta V, Sadjadian P, Al-Ali HK, Giraldo P, Guglielmelli P, Foltz L, Tavares R, Zaritskey A, Bouard C, Roncho JP, Tiwari R, Martino B (2017) Safety and efficacy of ruxolitinib (RUX) in elderly patients (≥ 75 years) with myelofibrosis (MF): an analysis from the phase 3b, expanded access JUMP study paper presented at the European Hematology Association Congress, Madrid, Spain, 22–25 June
69.
go back to reference Palandri F, Benevolo G, Palumbo A, Bonifacio M, Di Veroli A, Polverelli N, Andriani A, Tieghi A, Tiribelli M, Binotto G, Martino B, Petriccione L, D’Adda M, Crugnola M, Cavazzini F, Bergamaschi M, Isidori A, Trawinska M, Ibatici A, Bosi C, Sgherza N, Montanaro M, Breccia M, Sabattini E, Catani L, Vitolo U, Merli F, Aversa F, Vallisa D, Russo D, Semenzato P, Visani G, Fanin R, Cuneo A, Cavo M, Vianelli N, Latagliata R (2017) Efficacy and safety of ruxolitinib in elderly patients with myelofibrosis: a multicenter survey. Paper presented at the Italian Society of Haematology (SIE) conference, Rome, Italy, 15–18 October Palandri F, Benevolo G, Palumbo A, Bonifacio M, Di Veroli A, Polverelli N, Andriani A, Tieghi A, Tiribelli M, Binotto G, Martino B, Petriccione L, D’Adda M, Crugnola M, Cavazzini F, Bergamaschi M, Isidori A, Trawinska M, Ibatici A, Bosi C, Sgherza N, Montanaro M, Breccia M, Sabattini E, Catani L, Vitolo U, Merli F, Aversa F, Vallisa D, Russo D, Semenzato P, Visani G, Fanin R, Cuneo A, Cavo M, Vianelli N, Latagliata R (2017) Efficacy and safety of ruxolitinib in elderly patients with myelofibrosis: a multicenter survey. Paper presented at the Italian Society of Haematology (SIE) conference, Rome, Italy, 15–18 October
70.
go back to reference Breccia M, Tiribelli M, Bonifacio M, Palumbo A, Tieghi A, Polverelli N, Bergamaschi M, Cavazzini F, Isidori A, Binotto G, Cimino G, D’Adda M, Crugnola M, Bosi C, Sgherza N, Spinsanti M, Molica M, Fama A, Cerqui E, Lazzaro A, Scaffidi L, Colafigli G, Latagliata R, Fanin R, Russo D, Aversa F, Cuneo A, Cavo M, Vianelli N, Foa P, Palandri F (2017) Comorbidities and body mass index impact on survival in patients with myelofibrosis treated with ruxolitinib. Paper presented at the Italian Society of Haematology (SIE) conference, Rome, Italy, 15–18 October Breccia M, Tiribelli M, Bonifacio M, Palumbo A, Tieghi A, Polverelli N, Bergamaschi M, Cavazzini F, Isidori A, Binotto G, Cimino G, D’Adda M, Crugnola M, Bosi C, Sgherza N, Spinsanti M, Molica M, Fama A, Cerqui E, Lazzaro A, Scaffidi L, Colafigli G, Latagliata R, Fanin R, Russo D, Aversa F, Cuneo A, Cavo M, Vianelli N, Foa P, Palandri F (2017) Comorbidities and body mass index impact on survival in patients with myelofibrosis treated with ruxolitinib. Paper presented at the Italian Society of Haematology (SIE) conference, Rome, Italy, 15–18 October
71.
go back to reference Polverelli N, Binotto G, Palumbo A, Bonifacio M, Breccia M, Martino B, D’Adda M, Catani L, Sabattini E, Abruzzese E, Tiribelli M, Bergamaschi M, Sgherza N, Tieghi A, Benevolo G, Cavazzini F, Isidori A, Ibatici A, Heidel F, Crugnola M, Bosi C, Latagliata R, Russo D, Cavo M, Vianelli N, Palandri F (2017) Epidemiology, outcome and risk factors for infectious complications in MF patients receiving ruxolitinib. A multicenter study on 466 patients. Paper presented at the Italian Society of Haematology (SIE) conference, Rome, Italy, 15–18 October Polverelli N, Binotto G, Palumbo A, Bonifacio M, Breccia M, Martino B, D’Adda M, Catani L, Sabattini E, Abruzzese E, Tiribelli M, Bergamaschi M, Sgherza N, Tieghi A, Benevolo G, Cavazzini F, Isidori A, Ibatici A, Heidel F, Crugnola M, Bosi C, Latagliata R, Russo D, Cavo M, Vianelli N, Palandri F (2017) Epidemiology, outcome and risk factors for infectious complications in MF patients receiving ruxolitinib. A multicenter study on 466 patients. Paper presented at the Italian Society of Haematology (SIE) conference, Rome, Italy, 15–18 October
73.
75.
go back to reference Scherber R, Dueck AC, Johansson P, Barbui T, Barosi G, Vannucchi AM, Passamonti F, Andreasson B, Ferarri ML, Rambaldi A, Samuelsson J, Birgegard G, Tefferi A, Harrison CN, Radia D, Mesa RA (2011) The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF): international prospective validation and reliability trial in 402 patients. Blood 118(2):401–408. https://doi.org/10.1182/blood-2011-01-328955 PubMedCrossRef Scherber R, Dueck AC, Johansson P, Barbui T, Barosi G, Vannucchi AM, Passamonti F, Andreasson B, Ferarri ML, Rambaldi A, Samuelsson J, Birgegard G, Tefferi A, Harrison CN, Radia D, Mesa RA (2011) The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF): international prospective validation and reliability trial in 402 patients. Blood 118(2):401–408. https://​doi.​org/​10.​1182/​blood-2011-01-328955 PubMedCrossRef
76.
go back to reference Emanuel RM, Dueck AC, Geyer HL, Kiladjian JJ, Slot S, Zweegman S, te Boekhorst PA, Commandeur S, Schouten HC, Sackmann F, Kerguelen Fuentes A, Hernandez-Maraver D, Pahl HL, Griesshammer M, Stegelmann F, Doehner K, Lehmann T, Bonatz K, Reiter A, Boyer F, Etienne G, Ianotto JC, Ranta D, Roy L, Cahn JY, Harrison CN, Radia D, Muxi P, Maldonado N, Besses C, Cervantes F, Johansson PL, Barbui T, Barosi G, Vannucchi AM, Passamonti F, Andreasson B, Ferrari ML, Rambaldi A, Samuelsson J, Birgegard G, Tefferi A, Mesa RA (2012) Myeloproliferative neoplasm (MPN) symptom assessment form total symptom score: prospective international assessment of an abbreviated symptom burden scoring system among patients with MPNs. J Clin Oncol 30(33):4098–4103. https://doi.org/10.1200/JCO.2012.42.3863 PubMedCrossRefPubMedCentral Emanuel RM, Dueck AC, Geyer HL, Kiladjian JJ, Slot S, Zweegman S, te Boekhorst PA, Commandeur S, Schouten HC, Sackmann F, Kerguelen Fuentes A, Hernandez-Maraver D, Pahl HL, Griesshammer M, Stegelmann F, Doehner K, Lehmann T, Bonatz K, Reiter A, Boyer F, Etienne G, Ianotto JC, Ranta D, Roy L, Cahn JY, Harrison CN, Radia D, Muxi P, Maldonado N, Besses C, Cervantes F, Johansson PL, Barbui T, Barosi G, Vannucchi AM, Passamonti F, Andreasson B, Ferrari ML, Rambaldi A, Samuelsson J, Birgegard G, Tefferi A, Mesa RA (2012) Myeloproliferative neoplasm (MPN) symptom assessment form total symptom score: prospective international assessment of an abbreviated symptom burden scoring system among patients with MPNs. J Clin Oncol 30(33):4098–4103. https://​doi.​org/​10.​1200/​JCO.​2012.​42.​3863 PubMedCrossRefPubMedCentral
77.
go back to reference Efficace F, Baccarani M, Breccia M, Saussele S, Abel G, Caocci G, Guilhot F, Cocks K, Naeem A, Sprangers M, Oerlemans S, Chie W, Castagnetti F, Bombaci F, Sharf G, Cardoni A, Noens L, Pallua S, Salvucci M, Nicolatou-Galitis O, Rosti G, Mandelli F (2014) International development of an EORTC questionnaire for assessing health-related quality of life in chronic myeloid leukemia patients: the EORTC QLQ-CML24. Qual Life Res 23(3):825–836. https://doi.org/10.1007/s11136-013-0523-5 PubMedCrossRef Efficace F, Baccarani M, Breccia M, Saussele S, Abel G, Caocci G, Guilhot F, Cocks K, Naeem A, Sprangers M, Oerlemans S, Chie W, Castagnetti F, Bombaci F, Sharf G, Cardoni A, Noens L, Pallua S, Salvucci M, Nicolatou-Galitis O, Rosti G, Mandelli F (2014) International development of an EORTC questionnaire for assessing health-related quality of life in chronic myeloid leukemia patients: the EORTC QLQ-CML24. Qual Life Res 23(3):825–836. https://​doi.​org/​10.​1007/​s11136-013-0523-5 PubMedCrossRef
Metadata
Title
Identification and assessment of frailty in older patients with chronic myeloid leukemia and myelofibrosis, and indications for tyrosine kinase inhibitor treatment
Authors
Massimo Breccia
Francesca Palandri
Luigiana Luciano
Giulia Benevolo
Massimiliano Bonifacio
Giovanni Caocci
Fausto Castagnetti
Giuseppe A. Palumbo
Alessandra Iurlo
Francesco Landi
Publication date
01-05-2018
Publisher
Springer Berlin Heidelberg
Published in
Annals of Hematology / Issue 5/2018
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-018-3258-0

Other articles of this Issue 5/2018

Annals of Hematology 5/2018 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.