CML in the very elderly: the impact of comorbidities and TKI selection in a real-life multicenter study.
Chronic myeloid leukemia
Comorbidity
Drug toxicity
Geriatric oncology
Survival analysis
Treatment outcome
Tyrosine kinase inhibitors
Journal
Annals of hematology
ISSN: 1432-0584
Titre abrégé: Ann Hematol
Pays: Germany
ID NLM: 9107334
Informations de publication
Date de publication:
11 Jun 2024
11 Jun 2024
Historique:
received:
01
03
2024
accepted:
31
05
2024
medline:
12
6
2024
pubmed:
12
6
2024
entrez:
11
6
2024
Statut:
aheadofprint
Résumé
Tyrosine kinase inhibitors (TKIs) have greatly improved chronic myeloid leukemia (CML) treatments, with survival rates close to the general population. Yet, for the very elderly, robust data remains limited. This study focused on assessing comorbidities, treatment approaches, responses, and survival for elderly CML patients. Our study was conducted on 123 elderly (≥ 75 years) CML patients across four centers in Israel and Moffitt Cancer Center, USA. The median age at diagnosis was 79.1 years, with 44.7% being octogenarians. Comorbidities were very common; cardiovascular risk factors (60%), cardiovascular diseases (42%), with a median age-adjusted Charlson Comorbidity Index (aaCCI) of 5. Imatinib was the leading first-line therapy (69%), while the use of second-generation TKIs increased post-2010. Most patients achieved a major molecular response (MMR, 66.7%), and half achieved a deep molecular response (DMR, 50.4%). Over half (52.8%) of patients moved to second-line, and nearly a quarter (23.5%) to third-line treatments, primarily due to intolerance. Overall survival (OS) was notably longer in patients with an aaCCI score below 5, and in patients who attained DMR. Contrary to expectations, the Israeli cohort showed a shorter actual life expectancy than projected, suggesting a larger impact of CML on elderly survival. In summary, imatinib remains the main initial treatment, but second-generation TKIs are on the rise among elderly CML patients. Outcomes in elderly CML patients depend on comorbidities, TKI type, response, and age, underscoring the need for personalized therapy and additional research on TKI effectiveness and safety.
Identifiants
pubmed: 38862792
doi: 10.1007/s00277-024-05828-3
pii: 10.1007/s00277-024-05828-3
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s).
Références
Bower H, Björkholm M, Dickman PW, Höglund M, Lambert PC, Andersson TM (2016) Life Expectancy of Patients With Chronic Myeloid Leukemia Approaches the Life Expectancy of the General Population. J Clin Oncol 34(24):2851–2857. https://doi.org/10.1200/jco.2015.66.2866
doi: 10.1200/jco.2015.66.2866
pubmed: 27325849
Latagliata R, Breccia M, Carmosino I, Cannella L, De Cuia R, Diverio D, Frustaci A, Loglisci G, Mancini M, Santopietro M, Stefanizzi C, Volpicelli P, Vozella F, Alimena G (2010) “Real-life” results of front-line treatment with Imatinib in older patients (≥ 65 years) with newly diagnosed chronic myelogenous leukemia. Leuk Res 34(11):1472–1475. https://doi.org/10.1016/j.leukres.2010.07.001
doi: 10.1016/j.leukres.2010.07.001
pubmed: 20708799
Maas C, van Klaveren D, Ector G, Posthuma EFM, Visser O, Westerweel PE, Janssen J, Blijlevens NMA, Dinmohamed AG (2022) The evolution of the loss of life expectancy in patients with chronic myeloid leukaemia: a population-based study in the Netherlands, 1989–2018. Br J Haematol 196(5):1219–1224. https://doi.org/10.1111/bjh.17989
doi: 10.1111/bjh.17989
pubmed: 34865221
Pallera A, Altman JK, Berman E, Abboud CN, Bhatnagar B, Curtin P, DeAngelo DJ, Gotlib J, Hagelstrom RT, Hobbs G, Jagasia M, Kantarjian HM, Kropf P, Metheny L, Moore JO, Ontiveros E, Purev E, Quiery A, Reddy VV, Rose MG, Shah NP, Smith BD, Snyder DS, Sweet KL, Tibes R, Yang DT, Gregory K, Sundar H, Deininger M, Radich JP (2016) NCCN Guidelines Insights: Chronic Myeloid Leukemia, Version 1.2017. J Natl Compr Canc Netw 14(12):1505–1512. https://doi.org/10.6004/jnccn.2016.0162
doi: 10.6004/jnccn.2016.0162
pubmed: 27956535
Kanapuru B, Singh H, Myers A, Beaver J, Kwitkowski V, Farrell A, Pazdur R (2017) Enrollment of Older Adults in Clinical Trials Evaluating Patients with Hematologic Malignancies - the Food and Drug Administration (FDA) Experience. Blood 130:861–861. https://doi.org/10.1182/blood.V130.Suppl_1.861.861
doi: 10.1182/blood.V130.Suppl_1.861.861
Rohrbacher M, Berger U, Hochhaus A, Metzgeroth G, Adam K, Lahaye T, Saussele S, Müller MC, Hasford J, Heimpel H, Hehlmann R (2009) Clinical trials underestimate the age of chronic myeloid leukemia (CML) patients Incidence and median age of Ph/BCR-ABL-positive CML and other chronic myeloproliferative disorders in a representative area in Germany. Leukemia 23(3):602–604. https://doi.org/10.1038/leu.2008.245
doi: 10.1038/leu.2008.245
pubmed: 18784744
Latagliata R, Stagno F, Annunziata M, Abruzzese E, Iurlo A, Guarini A, Fava C, Gozzini A, Bonifacio M, Sorà F, LeonettiCrescenzi S, Bocchia M, Crugnola M, Castagnetti F, Capodanno I, Galimberti S, Feo C, Porrini R, Pregno P, Rizzo M, Antolino A, Mauro E, Sgherza N, Luciano L, Tiribelli M, Russo Rossi A, Trawinska M, Vigneri P, Breccia M, Rosti G, Alimena G (2016) Frontline Dasatinib Treatment in a “Real-Life” Cohort of Patients Older than 65 Years with Chronic Myeloid Leukemia. Neoplasia 18(9):536–540. https://doi.org/10.1016/j.neo.2016.07.005
doi: 10.1016/j.neo.2016.07.005
pubmed: 27659013
pmcid: 5031865
Luciano L, Latagliata R, Gugliotta G, Annunziata M, Tiribelli M, Martino B, Sica A, Esposito MR, Bocchia M, Galimberti S, Sorà F, Albano F, Palmieri R, Pregno P, Dragani M, Iovine M, Sica S, Iurlo A, Castagnetti F, Rosti G, Breccia M (2023) Efficacy and safety of nilotinib as frontline treatment in elderly (> 65 years) chronic myeloid leukemia patients outside clinical trials. Ann Hematol 102(6):1375–1382. https://doi.org/10.1007/s00277-023-05159-9
doi: 10.1007/s00277-023-05159-9
pubmed: 37079069
pmcid: 10182159
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. Ann Oncol 26(1):185–192. https://doi.org/10.1093/annonc/mdu490
doi: 10.1093/annonc/mdu490
pubmed: 25361995
Kelkitli E, Goker H, Turgut M, Atay H (2018) Analysis of Elderly Patients with Chronic Myeloid Leukemia. Blood 132:5449–5449. https://doi.org/10.1182/blood-2018-99-110222
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
doi: 10.1038/leu.2016.5
pubmed: 26837842
pmcid: 4858585
Coutinho AD, Makenbaeva D, Farrelly E, Landsman-Blumberg PB, Lenihan D (2017) Elevated Cardiovascular Disease Risk in Patients With Chronic Myelogenous Leukemia Seen in Community-based Oncology Practices in the United States. Clin Lymphoma Myeloma Leuk 17(10):676–683. https://doi.org/10.1016/j.clml.2017.06.011
doi: 10.1016/j.clml.2017.06.011
pubmed: 28729178
Gora-Tybor J, Sacha T, Wącław J, Niesiobędzka-Krężel J, Grzybowska-Izydorczyk O, Mędraś E, Dereń-Wagemann I, Patkowska E, Seferyńska I, Lewandowski K, Wache A, Blajer-Olszewska B, Wątek M, Kotwica-Mojzych K, Wasilewska E, Warzocha K, Jamroziak K (2018) Comorbidity Burden and Use of Concomitant Medications at CML Diagnosis: A Retrospective Analysis of 527 Patients From the Polish Adult Leukemia Group Registry. Clin Lymphoma Myeloma Leuk 18(7):e283–e285. https://doi.org/10.1016/j.clml.2018.05.001
doi: 10.1016/j.clml.2018.05.001
pubmed: 29778693
Crugnola M, Castagnetti F, Breccia M, Ferrero D, Trawinska MM, Abruzzese E, Annunziata M, Stagno F, Tiribelli M, Binotto G, Bonifacio M, Fava C, Iurlo A, Bucelli C, Mansueto G, Gozzini A, Falzetti F, Montefusco E, Crisà E, Gugliotta G, Russo S, Cedrone M, RussoRossi A, Pregno P, Isidori A, Mauro E, Atelda R, Giglio G, Celesti F, Sorà F, Storti S, D’Addosio A, Galimberti S, Orlandi E, Calistri E, Bocchia M, Cavazzini F, RegeCambrin G, Orofino N, Luciano L, Sgherza N, Rosti G, Latagliata R, Capodanno I (2019) Outcome of very elderly chronic myeloid leukaemia patients treated with imatinib frontline. Ann Hematol 98(10):2329–2338. https://doi.org/10.1007/s00277-019-03767-y
doi: 10.1007/s00277-019-03767-y
pubmed: 31392461
Hochhaus A, Baccarani M, Silver RT, Schiffer C, Apperley JF, Cervantes F, Clark RE, Cortes JE, Deininger MW, Guilhot F, Hjorth-Hansen H, Hughes TP, Janssen J, Kantarjian HM, Kim DW, Larson RA, Lipton JH, Mahon FX, Mayer J, Nicolini F, Niederwieser D, Pane F, Radich JP, Rea D, Richter J, Rosti G, Rousselot P, Saglio G, Saußele S, Soverini S, Steegmann JL, Turkina A, Zaritskey A, Hehlmann R (2020) European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia 34(4):966–984. https://doi.org/10.1038/s41375-020-0776-2
doi: 10.1038/s41375-020-0776-2
pubmed: 32127639
pmcid: 7214240
Brunner AM, Campigotto F, Sadrzadeh H, Drapkin BJ, Chen YB, Neuberg DS, Fathi AT (2013) Trends in all-cause mortality among patients with chronic myeloid leukemia: a Surveillance, Epidemiology, and End Results database analysis. Cancer 119(14):2620–2629. https://doi.org/10.1002/cncr.28106
doi: 10.1002/cncr.28106
pubmed: 23625575
Cortes JE, Talpaz M, Kantarjian H (1996) Chronic myelogenous leukemia: A review. Am J Med 100(5):555–570. https://doi.org/10.1016/S0002-9343(96)00061-7
doi: 10.1016/S0002-9343(96)00061-7
pubmed: 8644769
Sokal JE, Baccarani M, Russo D, Tura S (1988) Staging and prognosis in chronic myelogenous leukemia. Semin Hematol 25(1):49–61
pubmed: 3279515
Hasford J, Pfirrmann M, Hehlmann R, Allan NC, Baccarani M, Kluin-Nelemans JC, Alimena G, Steegmann JL, Ansari H (1998) A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. Writing Committee for the Collaborative CML Prognostic Factors Project Group. J Natl Cancer Inst 90(11):850–858. https://doi.org/10.1093/jnci/90.11.850
doi: 10.1093/jnci/90.11.850
pubmed: 9625174
Pfirrmann M, Clark RE, Prejzner W, Lauseker M, Baccarani M, Saussele S, Guilhot F, Heibl S, Hehlmann R, Faber E, Turkina A, Ossenkoppele G, Höglund M, Zaritskey A, Griskevicius L, Olsson-Strömberg U, Everaus H, Koskenvesa P, Labar B, Sacha T, Zackova D, Cervantes F, Colita A, Zupan I, Bogdanovic A, Castagnetti F, Guilhot J, Hasford J, Hochhaus A, Hoffmann VS (2020) The EUTOS long-term survival (ELTS) score is superior to the Sokal score for predicting survival in chronic myeloid leukemia. Leukemia 34(8):2138–2149. https://doi.org/10.1038/s41375-020-0931-9
doi: 10.1038/s41375-020-0931-9
pubmed: 32601376
pmcid: 7387299
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, ..., Rosti G (2015) Differences among young adults, adults and elderly chronic myeloid leukemia patients. Ann Oncol 26 (1):185–192. https://doi.org/10.1093/annonc/mdu490
Balducci L, Dolan D (2014) Chronic Myelogenous Leukemia (CML) in the elderly. Mediterr J Hematol Infect Dis 6(1):e2014037. https://doi.org/10.4084/mjhid.2014.037
doi: 10.4084/mjhid.2014.037
pubmed: 24959334
pmcid: 4063619
Caocci G, Mulas O, Annunziata M, Luciano L, Abruzzese E, Bonifacio M, Orlandi EM, Albano F, Galimberti S, Iurlo A, Pregno P, Sgherza N, Martino B, Binotto G, Castagnetti F, Gozzini A, Bocchia M, Fozza C, Stagno F, Simula MP, De Gregorio F, Trawinska MM, Scaffidi L, Elena C, Attolico I, Baratè C, Cattaneo D, Pirillo F, Gugliotta G, Sicuranza A, Molica M, La Nasa G, Foà R, Breccia M (2020) Long-term mortality rate for cardiovascular disease in 656 chronic myeloid leukaemia patients treated with second- and third-generation tyrosine kinase inhibitors. Int J Cardiol 301:163–166. https://doi.org/10.1016/j.ijcard.2019.10.036
doi: 10.1016/j.ijcard.2019.10.036
pubmed: 31711851
Jabbour E, Makenbaeva D, Lingohr-Smith M, Lin J (2015) Use of Real-World Claim Databases to Assess Prevalence of Comorbid Conditions Relevant to the Treatment of Chronic Myelogenous Leukemia Based on National Comprehensive Network Treatment Guidelines. Clin Lymphoma Myeloma Leuk 15(12):797–802. https://doi.org/10.1016/j.clml.2015.09.008
doi: 10.1016/j.clml.2015.09.008
pubmed: 26603185
Costa A, Abruzzese E, Latagliata R, Mulas O, Carmosino I, Scalzulli E, Bisegna ML, Ielo C, Martelli M, Caocci G, Breccia M (2024) Safety and Efficacy of TKIs in very Elderly Patients (≥75 Years) with Chronic Myeloid Leukemia. J Clin Med 13 (1). https://doi.org/10.3390/jcm13010273
Thielen N, Visser O, Ossenkoppele G, Janssen J (2016) Chronic myeloid leukemia in the Netherlands: a population-based study on incidence, treatment, and survival in 3585 patients from 1989 to 2012. Eur J Haematol 97(2):145–154. https://doi.org/10.1111/ejh.12695
doi: 10.1111/ejh.12695
pubmed: 26519944
Ector G, Visser O, Westerweel PE, Janssen J, Blijlevens NMA, Dinmohamed AG (2020) Primary therapy and relative survival among elderly patients with chronic myeloid leukemia: a population-based study in the Netherlands, 1989–2017. Leukemia 34(12):3408–3412. https://doi.org/10.1038/s41375-020-0902-1
doi: 10.1038/s41375-020-0902-1
pubmed: 32513966
Giles FJ, Rea D, Rosti G, Cross NCP, Steegmann JL, Griskevicius L, le Coutre P, Coriu D, Petrov L, Ossenkoppele GJ, Mahon FX, Saussele S, Hellmann A, Koskenvesa P, Brümmendorf TH, Gastl G, Castagnetti F, Vincenzi B, Haenig J, Hochhaus A (2017) Impact of age on efficacy and toxicity of nilotinib in patients with chronic myeloid leukemia in chronic phase: ENEST1st subanalysis. J Cancer Res Clin Oncol 143(8):1585–1596. https://doi.org/10.1007/s00432-017-2402-x
doi: 10.1007/s00432-017-2402-x
pubmed: 28364360
pmcid: 5504128
Cortes JE, Saglio G, Kantarjian HM, Baccarani M, Mayer J, Boqué C, Shah NP, Chuah C, Casanova L, Bradley-Garelik B, Manos G, Hochhaus A (2016) Final 5-Year Study Results of DASISION: The Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients Trial. J Clin Oncol 34(20):2333–2340. https://doi.org/10.1200/jco.2015.64.8899
doi: 10.1200/jco.2015.64.8899
pubmed: 27217448
pmcid: 5118045
Kantarjian HM, Hughes TP, Larson RA, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Boquimpani C, Pasquini R, Clark RE, Dubruille V, Flinn IW, Kyrcz-Krzemien S, Medras E, Zanichelli M, Bendit I, Cacciatore S, Titorenko K, Aimone P, Saglio G, Hochhaus A (2021) Long-term outcomes with frontline nilotinib versus imatinib in newly diagnosed chronic myeloid leukemia in chronic phase: ENESTnd 10-year analysis. Leukemia 35(2):440–453. https://doi.org/10.1038/s41375-020-01111-2
doi: 10.1038/s41375-020-01111-2
pubmed: 33414482
pmcid: 7862065
Garcia-Gutierrez V, Radich J, Hochhaus A, Saglio G, Masszi T, Hellmann A, Stentoft J, Casares M, Conneally E, Coutre P, Gattermann N, Martino B, Saussele S, Giles F, Aimone P, Li S, Titorenko K, Ross D (2020) Efficacy and Safety of Front-Line Nilotinib Treatment and Discontinuation in Older Patients (≥65 years) with Chronic Myeloid Leukemia in Chronic Phase Who Have Achieved MR4.5: Results from ENESTfreedom. Blood 136:7–8. https://doi.org/10.1182/blood-2020-137388
doi: 10.1182/blood-2020-137388
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
doi: 10.1056/NEJMoa0912614
pubmed: 20525993
Larson RA, Hochhaus A, Hughes TP, Clark RE, Etienne G, Kim DW, Flinn IW, Kurokawa M, Moiraghi B, Yu R, Blakesley RE, Gallagher NJ, Saglio G, Kantarjian HM (2012) Nilotinib vs imatinib in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: ENESTnd 3-year follow-up. Leukemia 26(10):2197–2203. https://doi.org/10.1038/leu.2012.134
doi: 10.1038/leu.2012.134
pubmed: 22699418