There are no studies analyzing how therapeutic changes impact on outcomes of older AML patients. This study analyzes patient´s and disease characteristics, treatment patterns, and outcomes of 3637 AML patients aged ≥60 years reported to the PETHEMA registry. Study periods were 1999–2006 (before hypomethylating agents-HMAs availability) vs 2007–2013, and treatments were intensive chemotherapy (IC), non-intensive, clinical trial (CT), and supportive care only (SC). Median age was 72 (range, 60–99), 57% male, median ECOG 1 (range, 0–4), secondary AML 914 (30%), with adverse-risk genetic in 720 (32%). Treatment differed between study periods (1999–2006 vs 2007–2013): IC 58% vs 32%, non-intensive 1 vs 23%, CT 0 vs 2%, SC 27 vs 28% (p < 0.001). Median OS was 4.7 months (1-year OS 29% and 5-years 7%, without differences between periods), 1.2 for SC, 7.8 for non-intensive, 8.6 for IC, and 10.4 for CT (p < 0.001). OS improved in the 2007–2013 period for IC patients (10.3 vs 7.5 months, p = 0.004), but worsened for SC patients (1.2 vs 1.6 months, p = 0.03). Our real-life study shows that, despite evolving treatment for elderly patients during the last decade, OS has remained unchanged. Epidemiologic registries will critically assess whether novel therapies lead to noteworthy advances in the near future (#NCT02606825).
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Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129:424–47.
Tallman MS, Wang ES, Altman JK, Appelbaum FR, Bhatt VR, Bixby D et al. Acute Myeloid Leukemia, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Cancer Netw. 2019. https://doi.org/10.6004/jnccn.2019.0028.
DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019;133:7–17.
Wei AH, Montesinos P, Ivanov V, DiNardo CD, Novak J, Laribi K, et al. Venetoclax plus LDAC for patients with untreated AML ineligible for intensive chemotherapy: phase 3 randomized placebo-controlled trial. Blood. 2020;135:2137–45.
DiNardo CD, Stein EM, De Botton S, Roboz GJ, Altman JK, Mims AS, et al. Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML. N Engl J Med. 2018;378:2386–98.
Cortes JE, Heidel FH, Hellmann A, Fiedler W, Smith BD, Robak T, et al. Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Leukemia. 2019;33:379–89.
Megías-Vericat JE, Ballesta-López O, Barragán E, Martínez-Cuadrón D, Montesinos P. Tyrosine kinase inhibitors for acute myeloid leukemia: a step toward disease control? Blood Rev. 2020. https://doi.org/10.1016/j.blre.2020.100675.
Bell JA, Galaznik A, Farrelly E, Blazer M, Murty S, Ogbonnaya A, et al. A retrospective study evaluating treatment patterns and survival outcomes in elderly patients with acute myeloid leukemia treated in the United States with either 7+3 or a hypomethylating agent. Leuk Res. 2019;78:45–51.
Juliusson G, Antunovic P, Derolf A, Lehmann S, Mollgard L, Stockelberg D, et al. Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry. Blood. 2009;113:4179–87.
Lowenberg B, Zittoun R, Kerkhofs H, Jehn U, Abels J, Debusscher L, et al. On the value of intensive remission-induction chemotherapy in elderly patients of 65+ years with acute myeloid leukemia: a randomized phase III study of the European Organization for Research and Treatment of Cancer Leukemia Group. J Clin Oncol. 1989;7:1268–74.
Murthy VH, Krumholz HM, Gross CP. Participation in cancer clinical trials: race-, sex-, and age-based disparities. J Am Med Assoc. 2004;291:2720–6.
Hutchins LF, Unger JM, Crowley JJ, Coltman CA, Albain KS. Underrepresentation of patients 65 years of age or older in cancer- treatment trials. N Engl J Med. 1999;341:2061–7.
Kalin B, Pijnappel EN, van Gelder M, Visser O, van de Loosdrecht AA, Ossenkoppele GJ, et al. Intensive treatment and trial participation in elderly acute myeloid leukemia patients: a population-based analysis in The Netherlands. Cancer Epidemiol. 2018;57:90–96.
Appelbaum FR, Gundacker H, Head DR, Slovak ML, Willman CL, Godwin JE, et al. Age and acute myeloid leukemia. Blood. 2006;107:3491–3485.
Mengis C, Aebi S, Tobler A, Dähler W, Fey MF. Assessment of differences in patient populations selected for or excluded from participation in clinical phase III acute myelogenous leukemia trials. J Clin Oncol. 2003;21:3933–9.
Grimwade D, Walker H, Harrison G, Oliver F, Chatters S, Harrison CJ, et al. The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): Analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial. Blood. 2001;98:1312–20.
Colovic M, Colovic N, Radojkovic M, Stanisavljevic D, Kraguljac N, Jankovic G, et al. Induction chemotherapy versus palliative treatment for acute myeloid leukemia in a consecutive cohort of elderly patients. Ann Hematol. 2012;91:1363–70.
Menzin J, Lang K, Earle CC, Kerney D, Mallick R. The outcomes and costs of acute myeloid leukemia among the elderly. Arch Intern Med. 2002;162:1597–603.
Taylor PRA, Reid MM, Stark AN, Bown N, Hamilton PJ, Proctor SJ. De novo acute myeloid leukaemia in patients over 55-years-old: a population-based study of incidence, treatment and outcome. Leukemia. 1995;9:231–7.
Juliusson G, Hagberg O, Lazarevic VL, Ölander E, Antunovic P, Cammenga J, et al. Improved survival of men 50 to 75 years old with acute myeloid leukemia over a 20-year period. Blood. 2019;134:1558–61.
Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015;126:291–9.
Kantarjian HM, Thomas XG, Dmoszynska A, Wierzbowska A, Mazur G, Mayer J, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012;30:2670–7.
Nagel G, Weber D, Fromm E, Erhardt S, Lübbert M, Fiedler W, et al. Epidemiological, genetic, and clinical characterization by age of newly diagnosed acute myeloid leukemia based on an academic population-based registry study (AMLSG BiO). Ann Hematol. 2017;96:1993–2003.
Oran B, Weisdorf DJ. Survival for older patients with acute myeloid leukemia: a population-based study. Haematologica. 2012;97:1916–24.
Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH, et al. Refinement of cytogenetic classification in AML Younger adult patients treated in UKMRC. Blood. 2010;116:354–66.
Cheson BD, Bennett JM, Kopecky KJ, Büchner T, Willman CL, Estey EH, et al. Revised Recommendations of the International Working Group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol. 2003;21:4642–9.
Kaplan EL, Meier P. Nonparametric Estimation from Incomplete Observations. J Am Stat Assoc. 1958;53:457–81.
Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep. 1966;50:163–70.
Bertoli S, Tavitian S, Huynh A, Borel C, Guenounou S, Luquet I, et al. Improved outcome for AML patients over the years 2000–14. Blood Cancer J. 2017;7:635.
Talati C, Dhulipala VC, Extermann M, Al Ali N, Kim J, Komrokji R, et al. Comparisons of commonly used front-line regimens on survival outcomes in patients aged 70 years and older with acute myeloid leukemia. Haematologica. 2020;105:398–406.
Medeiros BC, Satram-Hoang S, Hurst D, Hoang KQ, Momin F, Reyes C. Big data analysis of treatment patterns and outcomes among elderly acute myeloid leukemia patients in the United States. Ann Hematol. 2015;94:1127–38.
Juliusson G, Lazarevic V, Hörstedt AS, Hagberg O, Höglund M. Acute myeloid leukemia in the real world: why population-based registries are needed. Blood. 2012;119:3890–9.
Juliusson G, Jädersten M, Deneberg S, Lehmann S, Mollgard L, Wennstrom L, et al. The prognostic impact of FLT3-ITD and NPM1 mutation in adult AML is age-dependent in the population-based setting. Blood Adv. 2020;4:1094–101.
Lazarevic VL, Bredberg A, Lorenz F, Öhlander E, Antunovic P, Cammenga J, et al. Acute myeloid leukemia in very old patients. Haematologica. 2018;103:e578–e580.
Faderl S, Ravandi F, Huang X, Wang X, Jabbour E, Garcia-Manero G, et al. Clofarabine plus low-dose cytarabine followed by clofarabine plus low-dose cytarabine alternating with decitabine in acute myeloid leukemia frontline therapy for older patients. Cancer. 2012;118:4471–7.
Kadia TM, Cortes J, Ravandi F, Jabbour E, Konopleva M, Benton CB, et al. Cladribine and low-dose cytarabine alternating with decitabine as front-line therapy for elderly patients with acute myeloid leukaemia: a phase 2 single-arm trial. Lancet Haematol. 2018;5:e411–e421.
Pleyer L, Döhner H, Dombret H, Seymour JF, Schuh AC, Beach CL, et al. Azacitidine for front-line therapy of patients with AML: reproducible efficacy established by direct comparison of international phase 3 trial data with registry data from the austrian azacitidine registry of the AGMT study group. Int J Mol Sci. 2017;18:415.
Falantes J, Pleyer L, Thépot S, Almeida AM, Maurillo L, Martínez-Robles V, et al. Real life experience with frontline azacitidine in a large series of older adults with acute myeloid leukemia stratified by MRC/LRF score: results from the expanded international E-ALMA series (E-ALMA+). Leuk Lymphoma. 2018;59:1113–20.
Maurillo L, Buccisano F, Spagnoli A, Voso MT, Fianchi L, Papayannidis C, et al. Comparative analysis of azacitidine and intensive chemotherapy as front-line treatment of elderly patients with acute myeloid leukemia. Ann Hematol. 2018;97:1767–74.
Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, et al. Cpx-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018;36:2684–92.
Wei AH, Strickland SA, Hou JZ, Fiedler W, Lin TL, Walter RB, et al. Venetoclax combined with low-dose cytarabine for previously untreated patients with acute myeloid leukemia: Results from a phase Ib/II study. J Clin Oncol. 2019;37:1277–84.
Shallis RM, Wang R, Davidoff A, Ma X, Zeidan AM. Epidemiology of acute myeloid leukemia: recent progress and enduring challenges. Blood Rev. 2019;36:70–87.
Bertoli S, Tavitian S, Bories P, Luquet I, Delabesse E, Comont T, et al. Outcome of patients aged 60-75 years with newly diagnosed secondary acute myeloid leukemia: a single-institution experience. Cancer Med. 2019;8:3846–54.
Muffly L, Pasquini MC, Martens M, Brazauskas R, Zhu X, Adekola K, et al. Increasing use of allogeneic hematopoietic cell transplantation in patients aged 70 years and older in the United States. Blood. 2017;130:1156–64.
The authors would like to thank María D. García, Carlos Pastorini, and Mar Benlloch for data collection and management. This study was supported in part by Janssen Pharmaceutica, and the Cooperative Research Thematic Network (RTICC) (Grant RD12/0036/014 (ISCIII & ERDF).
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Martínez-Cuadrón, D., Serrano, J., Gil, C. et al. Evolving treatment patterns and outcomes in older patients (≥60 years) with AML: changing everything to change nothing?. Leukemia (2020). https://doi.org/10.1038/s41375-020-01058-4
American Journal of Hematology (2020)