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Patterns of Care and Survival for Elderly Acute Myeloid Leukemia—Challenges and Opportunities

  • Health Economics (N Khera, Section Editor)
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Abstract

Purpose of Review

Acute myeloid leukemia (AML) is a disease of the elderly, with a median age of diagnosis in the sixth decade of life. Mortality has declined over the last few years, but this impact is apparent only in the young, fit AML population. Outcomes for the elderly remain poor, with less than 20% 5-year overall survival rates. Hence, there is an unmet need to identify treatment strategies to maximize benefit in this age group.

Recent Findings

Elderly AML is a difficult entity to treat due to both disease and patient-related factors. Treatment of this group has a lot of inter-physician and inter-institutional variability. Several objective criteria to assess biological age, impact of co-morbidities, and fitness have been published, which could be utilized to make management decisions. For old and unfit AML patients, a variety of novel therapeutic agents are currently being investigated.

Summary

Objective analysis of biological age should include assessment of fitness, frailty, and co-morbidities in elderly AML. Future areas of research include development of an objective risk-based approach and its validation in clinical trials, development of novel therapeutic agents, and improvement in supportive care measures.

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References

  1. Appelbaum FR, Gundacker H, Head DR, Slovak ML, Willman CL, Godwin JE, et al. Age and acute myeloid leukemia. Blood. 2006;107(9):3481–5. doi:10.1182/blood-2005-09-3724.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Burnett AK, Russell N, Hills RK, Panoskaltsis N, Khwaja A, Hemmaway C, et al. A randomised comparison of the novel nucleoside analogue sapacitabine with low-dose cytarabine in older patients with acute myeloid leukaemia. Leukemia. 2015;29(6):1312–9. doi:10.1038/leu.2015.38.

    Article  CAS  PubMed  Google Scholar 

  3. Foran JM, Sun Z, Claxton DF, Lazarus HM, Thomas ML, Melnick A, et al. North American leukemia, intergroup phase III randomized trial of single agent clofarabine as induction and post-remission therapy, and decitabine as maintenance therapy in newly-diagnosed acute myeloid leukemia in older adults (age ≥60 years): a trial of the ECOG-ACRIN Cancer Research Group (E2906). Blood. 2015;126(23):217.

    Google Scholar 

  4. Stone RM, Berg DT, George SL, Dodge RK, Paciucci PA, Schulman PP, et al. Postremission therapy in older patients with de novo acute myeloid leukemia: a randomized trial comparing mitoxantrone and intermediate-dose cytarabine with standard-dose cytarabine. Blood. 2001;98(3):548–53.

    Article  CAS  PubMed  Google Scholar 

  5. Burnett AK. Treatment of acute myeloid leukemia: are we making progress? Hematology Am Soc Hematol Educ Program. 2012;2012:1–6. doi:10.1182/asheducation-2012.1.1.

    PubMed  Google Scholar 

  6. Complete reference for line 520 (This is a web reference): National Comprehensive Cancer Network. Acute Myeloid Leukemia (Version 2.2016). https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf. Accessed June 29th, 2016.

  7. Dohner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Buchner T, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424–47. doi:10.1182/blood-2016-08-733196.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Krug U, Rollig C, Koschmieder A, Heinecke A, Sauerland MC, Schaich M, et al. Complete remission and early death after intensive chemotherapy in patients aged 60 years or older with acute myeloid leukaemia: a web-based application for prediction of outcomes. Lancet. 2010;376(9757):2000–8. doi:10.1016/s0140-6736(10)62105-8.

    Article  CAS  PubMed  Google Scholar 

  9. Pastore F, Dufour A, Benthaus T, Metzeler KH, Maharry KS, Schneider S, et al. Combined molecular and clinical prognostic index for relapse and survival in cytogenetically normal acute myeloid leukemia. J Clin Oncol. 2014;32(15):1586–94. doi:10.1200/jco.2013.52.3480.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Mohamed I, Hills RK, Burnett AK. Who is an “older” patient with acute myeloid leukaemia (AML)? An investigation of two NCRI/AML trials. Br J Haematol. 2014;165(1):147–51. doi:10.1111/bjh.12705.

    Article  PubMed  Google Scholar 

  11. Artz AS. Biologic vs physiologic age in the transplant candidate. Hematology Am Soc Hematol Educ Program. 2016;2016(1):99–105. doi:10.1182/asheducation-2016.1.99.

    PubMed  Google Scholar 

  12. Walter RB, Othus M, Borthakur G, Ravandi F, Cortes JE, Pierce SA, et al. Prediction of early death after induction therapy for newly diagnosed acute myeloid leukemia with pretreatment risk scores: a novel paradigm for treatment assignment. J Clin Oncol. 2011;29(33):4417–23. doi:10.1200/jco.2011.35.7525.

    Article  PubMed  PubMed Central  Google Scholar 

  13. 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(18):4179–87. doi:10.1182/blood-2008-07-172007.

    Article  CAS  PubMed  Google Scholar 

  14. 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(14):1597–603.

    Article  PubMed  Google Scholar 

  15. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Gattermann N, Germing U, et al. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol. 2010;28(4):562–9. doi:10.1200/jco.2009.23.8329.

    Article  CAS  PubMed  Google Scholar 

  16. Stein RS, Vogler WR, Winton EF, Cohen HJ, Raney MR, Bartolucci A. Therapy of acute myelogenous leukemia in patients over the age of 50: a randomized Southeastern Cancer Study Group trial. Leuk Res. 1990;14(10):895–903.

    Article  CAS  PubMed  Google Scholar 

  17. Rao AV, Valk PJ, Metzeler KH, Acharya CR, Tuchman SA, Stevenson MM, et al. Age-specific differences in oncogenic pathway dysregulation and anthracycline sensitivity in patients with acute myeloid leukemia. J Clin Oncol. 2009;27(33):5580–6. doi:10.1200/jco.2009.22.2547.

    Article  CAS  PubMed  Google Scholar 

  18. Legrand O, Simonin G, Beauchamp-Nicoud A, Zittoun R, Marie JP. Simultaneous activity of MRP1 and Pgp is correlated with in vitro resistance to daunorubicin and with in vivo resistance in adult acute myeloid leukemia. Blood. 1999;94(3):1046–56.

    CAS  PubMed  Google Scholar 

  19. Garrido SM, Cooper JJ, Appelbaum FR, Willman CL, Kopecky K, Banker DE. Blasts from elderly acute myeloid leukemia patients are characterized by low levels of culture- and drug-induced apoptosis. Leuk Res. 2001;25(1):23–32.

    Article  CAS  PubMed  Google Scholar 

  20. Prebet T, Boissel N, Reutenauer S, Thomas X, Delaunay J, Cahn JY, et al. Acute myeloid leukemia with translocation (8;21) or inversion (16) in elderly patients treated with conventional chemotherapy: a collaborative study of the French CBF-AML intergroup. J Clin Oncol. 2009;27(28):4747–53. doi:10.1200/jco.2008.21.0674.

    Article  PubMed  Google Scholar 

  21. Sekeres MA, Stone RM, Zahrieh D, Neuberg D, Morrison V, De Angelo DJ, et al. Decision-making and quality of life in older adults with acute myeloid leukemia or advanced myelodysplastic syndrome. Leukemia. 2004;18(4):809–16. doi:10.1038/sj.leu.2403289.

    Article  CAS  PubMed  Google Scholar 

  22. Oliva EN, Nobile F, Alimena G, Ronco F, Specchia G, Impera S, et al. Quality of life in elderly patients with acute myeloid leukemia: patients may be more accurate than physicians. Haematologica. 2011;96(5):696–702. doi:10.3324/haematol.2010.036715.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Deschler B, Ihorst G, Platzbecker U, Germing U, Marz E, de Figuerido M, et al. Parameters detected by geriatric and quality of life assessment in 195 older patients with myelodysplastic syndromes and acute myeloid leukemia are highly predictive for outcome. Haematologica. 2013;98(2):208–16. doi:10.3324/haematol.2012.067892.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Lowenberg B, Suciu S, Archimbaud E, Haak H, Stryckmans P, de Cataldo R, et al. Mitoxantrone versus daunorubicin in induction-consolidation chemotherapy—the value of low-dose cytarabine for maintenance of remission, and an assessment of prognostic factors in acute myeloid leukemia in the elderly: final report. European Organization for the Research and Treatment of Cancer and the Dutch-Belgian Hemato-Oncology Cooperative Hovon Group. J Clin Oncol. 1998;16(3):872–81. doi:10.1200/jco.1998.16.3.872.

    Article  CAS  PubMed  Google Scholar 

  25. Goldstone AH, Burnett AK, Wheatley K, Smith AG, Hutchinson RM, Clark RE. Attempts to improve treatment outcomes in acute myeloid leukemia (AML) in older patients: the results of the United Kingdom Medical Research Council AML11 trial. Blood. 2001;98(5):1302–11.

    Article  CAS  PubMed  Google Scholar 

  26. Wetzler M, Mrozek K, Kohlschmidt J, Dombret H, Dohner H, Pilorge S, et al. Intensive induction is effective in selected octogenarian acute myeloid leukemia patients: prognostic significance of karyotype and selected molecular markers used in the European LeukemiaNet classification. Haematologica. 2014;99(2):308–13. doi:10.3324/haematol.2013.092072.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. 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(21):2670–7. doi:10.1200/jco.2011.38.9429.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. 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(3):291–9. doi:10.1182/blood-2015-01-621664.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Welch JS, Petti AA, Miller CA, Fronick CC, O’Laughlin M, Fulton RS, et al. TP53 and decitabine in acute myeloid leukemia and myelodysplastic syndromes. N Engl J Med. 2016;375(21):2023–36. doi:10.1056/NEJMoa1605949.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Pigneux A, Bene MC, Guardiola P, Recher C, Hamel JF, Sauvezie M, et al. Addition of androgens improves survival in elderly patients with acute myeloid leukemia: a GOELAMS study. J Clin Oncol. 2017;35(4):387–93. doi:10.1200/jco.2016.67.6213.

    Article  PubMed  Google Scholar 

  31. Fehniger TA, Uy GL, Trinkaus K, Nelson AD, Demland J, Abboud CN, et al. A phase 2 study of high-dose lenalidomide as initial therapy for older patients with acute myeloid leukemia. Blood. 2011;117(6):1828–33. doi:10.1182/blood-2010-07-297143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ustun C, Lazarus HM, Weisdorf D. To transplant or not: a dilemma for treatment of elderly AML patients in the twenty-first century. Bone Marrow Transplant. 2013;48(12):1497–505. doi:10.1038/bmt.2013.67.

    Article  CAS  PubMed  Google Scholar 

  33. Sorror ML, Sandmaier BM, Storer BE, Franke GN, Laport GG, Chauncey TR, et al. Long-term outcomes among older patients following nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation for advanced hematologic malignancies. JAMA. 2011;306(17):1874–83. doi:10.1001/jama.2011.1558.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Majhail NS, Brunstein CG, Shanley R, Sandhu K, McClune B, Oran B, et al. Reduced-intensity hematopoietic cell transplantation in older patients with AML/MDS: umbilical cord blood is a feasible option for patients without HLA-matched sibling donors. Bone Marrow Transplant. 2012;47(4):494–8. doi:10.1038/bmt.2011.114.

    Article  CAS  PubMed  Google Scholar 

  35. Chevallier P, Szydlo RM, Blaise D, Tabrizi R, Michallet M, Uzunov M, et al. Reduced-intensity conditioning before allogeneic hematopoietic stem cell transplantation in patients over 60 years: a report from the SFGM-TC. Biol Blood Marrow Transplant. 2012;18(2):289–94. doi:10.1016/j.bbmt.2011.07.013.

    Article  PubMed  Google Scholar 

  36. Koreth J, Aldridge J, Kim HT, Alyea EP 3rd, Cutler C, Armand P, et al. Reduced-intensity conditioning hematopoietic stem cell transplantation in patients over 60 years: hematologic malignancy outcomes are not impaired in advanced age. Biol Blood Marrow Transplant. 2010;16(6):792–800. doi:10.1016/j.bbmt.2009.12.537.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Koreth J, Schlenk R, Kopecky KJ, Honda S, Sierra J, Djulbegovic BJ, et al. Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials. JAMA. 2009;301(22):2349–61. doi:10.1001/jama.2009.813.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Michelis FV, Gupta V, Zhang MJ, Wang HL, Aljurf M, Bacher U, et al. Cytogenetic risk determines outcomes after allogeneic transplantation in older patients with acute myeloid leukemia in their second complete remission: a Center for International Blood and Marrow Transplant Research cohort analysis. Cancer. 2017; doi:10.1002/cncr.30567.

  39. Sorror ML, Maris MB, Storer B, Sandmaier BM, Diaconescu R, Flowers C, et al. Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative and myeloablative conditioning: influence of pretransplantation comorbidities. Blood. 2004;104(4):961–8. doi:10.1182/blood-2004-02-0545.

    Article  CAS  PubMed  Google Scholar 

  40. Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106(8):2912–9. doi:10.1182/blood-2005-05-2004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146–56.

    Article  CAS  PubMed  Google Scholar 

  42. Holmes HM, Des Bordes JK, Kebriaei P, Yennu S, Champlin RE, Giralt S, et al. Optimal screening for geriatric assessment in older allogeneic hematopoietic cell transplantation candidates. J Geriatr Oncol. 2014;5(4):422–30. doi:10.1016/j.jgo.2014.04.004.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Rao AV. Fitness in the elderly: how to make decisions regarding acute myeloid leukemia induction. Hematology Am Soc Hematol Educ Program. 2016;2016(1):339–47. doi:10.1182/asheducation-2016.1.339.

    PubMed  Google Scholar 

  44. Hurria A, Cirrincione CT, Muss HB, Kornblith AB, Barry W, Artz AS, et al. Implementing a geriatric assessment in cooperative group clinical cancer trials: CALGB 360401. J Clin Oncol. 2011;29(10):1290–6. doi:10.1200/jco.2010.30.6985.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Medeiros BC, Lancet JE, Cortes JE, Newell LF, Lin TL, Ritchie EK, et al. Analysis of efficacy by age for patients aged 60-75 with untreated secondary acute myeloid leukemia (AML) treated with CPX-351 liposome injection versus conventional cytarabine and daunorubicin in a phase III trial. Blood. 2016;128(22):902.

    Google Scholar 

  46. Ravandi F, Ritchie EK, Sayar H, Lancet JE, Craig MD, Vey N, et al. Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study. Lancet Oncol. 2015;16(9):1025–36. doi:10.1016/s1470-2045(15)00201-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Daver N. Long term survival and clinical complete responses of various prognostic subgroups in 103 relapsed/refractory acute myeloid leukemia (r/r AML) patients treated with guadecitabine (SGI-110). Blood. 2016.

  48. Eytan M. Stein JKA, Robert Collins, Daniel J DeAngelo, Amir T Fathi, Ian Flinn et al. AG-221, an oral, selective, first-in-class, potent inhibitor of the IDH2 mutant metabolic enzyme, induces durable remissions in a phase I study in patients with IDH2 mutation positive advanced hematologic malignancies (Abstract). Blood. 2014;2014(124:115).

  49. Stéphane de Botton DAP, Eytan M Stein, Courtney DiNardo, Amir T Fathi, Gail J Roboz, Robert Collins, Ronan T Swords, Ian Flinn, Jessica K Altman, Martin S Tallman, Hagop Kantarjian, Katelyn Colby, Bin Fan, Meredith Goldwasser, Malia Prahl, Sam Agresta, Richard M Stone. Clinical safety and activity of AG-120, a first-in-class, potent inhibitor of the IDH-1 mutant protein, in a phase 1 study of patients with advanced IDH1-mutant hematologic malignancies. EHA abstract. 2015.

  50. Cooper BW, Kindwall-Keller TL, Craig MD, Creger RJ, Hamadani M, Tse WW, et al. A phase I study of midostaurin and azacitidine in relapsed and elderly AML patients. Clin Lymphoma Myeloma Leuk. 2015;15(7):428–432 e2. doi:10.1016/j.clml.2015.02.017.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Cortes JE, Perl AE, Dombret H, Kayser S, Steffen B, Rousselot P, et al. Final results of a phase 2 open-label, monotherapy efficacy and safety study of quizartinib (AC220) in patients ≥ 60 years of age with FLT3 ITD positive or negative relapsed/refractory acute myeloid leukemia. Blood. 2012;120(21):48.

    Google Scholar 

  52. Uy GL, Mandrekar S, Laumann K, Sanford B, Marcucci G, Zhao W, et al. Addition of sorafenib to chemotherapy improves the overall survival of older adults with FLT3-ITD mutated acute myeloid leukemia (AML) (alliance C11001). Blood. 2015;126(23):319.

    Google Scholar 

  53. Bixby DL, Stein AS, Fathi AT, Kovacsovics TJ, Levy MY, Erba HP, et al. Vadastuximab talirine monotherapy in older patients with treatment naive CD33-positive acute myeloid leukemia (AML). Blood. 2016;128(22):590.

    Google Scholar 

  54. Montalban-Bravo G, Huang X, Naqvi K, Jabbour E, Borthakur G, DiNardo CD, et al. A clinical trial for patients with acute myeloid leukemia or myelodysplastic syndromes not eligible for standard clinical trials. Leukemia. 2017; doi:10.1038/leu.2017.85.

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  1. Department of Hematology, Mayo Clinic, 200 1st street SW, Rochester, MN, 55905, USA

    Abhishek A. Mangaonkar & Mrinal M. Patnaik

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  1. Abhishek A. Mangaonkar
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Mangaonkar, A.A., Patnaik, M.M. Patterns of Care and Survival for Elderly Acute Myeloid Leukemia—Challenges and Opportunities. Curr Hematol Malig Rep 12, 290–299 (2017). https://doi.org/10.1007/s11899-017-0388-8

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