Feasibility and Outcome of a Phase II Study of Intensive Induction Chemotherapy in 91 Elderly Patients with AML Evaluated Using a Simplified Multidimensional Geriatric Assessment.
Aged
Amifostine
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Cytarabine
/ administration & dosage
Feasibility Studies
Female
Gemtuzumab
/ administration & dosage
Geriatric Assessment
/ methods
Hematopoietic Stem Cell Transplantation
/ methods
Humans
Idarubicin
/ administration & dosage
Induction Chemotherapy
/ methods
Leukemia, Myeloid, Acute
/ drug therapy
Male
Middle Aged
Outcome Assessment, Health Care
Survival Analysis
Acute myeloid leukaemia (AML)
Autologous transplant (ASCT)
Elderly
Gemtuzumab ozogamicin (GO)
Multidimensional geriatric assessment (MGA)
Oncology
Journal
Advances in therapy
ISSN: 1865-8652
Titre abrégé: Adv Ther
Pays: United States
ID NLM: 8611864
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
03
02
2020
pubmed:
17
4
2020
medline:
15
12
2020
entrez:
17
4
2020
Statut:
ppublish
Résumé
We prospectively tested in a phase II study high-dose aracytin and idarubicin plus amifostine as induction regimen in 149 patients with acute myeloid leukaemia (AML) aged ≥ 60 years, evaluated by a simplified multidimensional geriatric assessment (MGA). Ninety-one fully or partially fit patients (61%) were allocated to intensive chemotherapy and 58 (39%) frail patients to best supportive care (BSC). Intensively treated patients, showing early death and complete response (CR) rate respectively of 5.5% and 73.6%, received 61 consolidations, followed by autologous transplant (ASCT), stem cell transplantation (SCT) or gemtuzumab ozogamicin, depending on mobilization outcome and donor availability. The 8-year overall survival (OS) of these patients was 20.4%, with median duration of 11.4 months significantly superior to the 1.5 months of BSC arm (p < 0.001). Hyperleukocytosis and cytogenetics were predictors of survival with a relative risk of 1.8 in patients with poor karyotype without hyperleukocytosis (p = 0.02) and 3 in those with hyperleukocytosis (≥ 50,000/μl) (p = 0.002). MGA allowed tailored post-consolidation in 53.8% of patients after high-dose aracytin induction, with long-term survival doubling that reported in the literature after standard-dose cytarabine regimens. The study was registered with the Umin Clinical Trial Registry (www.umin.ac.jp/ctr), number R000014052.
Identifiants
pubmed: 32297279
doi: 10.1007/s12325-020-01310-4
pii: 10.1007/s12325-020-01310-4
pmc: PMC7467471
doi:
Substances chimiques
Cytarabine
04079A1RDZ
Gemtuzumab
93NS566KF7
Amifostine
M487QF2F4V
Idarubicin
ZRP63D75JW
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
2288-2302Références
Farag SS, Archer KJ, Mrozek K, et al. Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia: results from cancer and leukemia group B 8461. Cancer and Leukemia Group B 8461. Blood. 2006;108:63–73.
pubmed: 16522815
pmcid: 1895823
Fröhling S, Schlenk RF, Kayser S, et al. Cytogenetics and age are the major determinants of outcome in intensively treated acute myeloid leukemia patients older than 60 years: results from the AMLSG trial AML HD98-B. Blood. 2006;108:3280–8.
pubmed: 16840728
Balducci L. Aging, frailty, and chemotherapy. Cancer Control. 2007;14:7–12.
pubmed: 17242666
Klepin HD, Balducci L. Acute myelogenous leukemia in older adults. Oncologist. 2009;14:222–32.
pubmed: 19282349
Godwin JE, Smith SE. Acute myeloid leukemia in the older patient. Crit Rev Oncol Hematol. 2003;48:S17–26.
pubmed: 14563517
Grimwade D, Walker H, Harrison G, 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.
pubmed: 11520776
Leith CP, Kopecky KJ, Godwin J, et al. Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy. A Southwest Oncology Group study. Blood. 1997;89:3323–9.
pubmed: 9129038
Löwenberg B, Ossenkoppele GJ, van Putten W, et al. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009;361:1235–48.
pubmed: 19776405
Ossenkoppele GJ, Graveland WJ, Sonneveld P, et al. The value of fludarabine in addition to ARA-C and G-CSF in the treatment of patients with high-risk myelodysplastic syndromes and AML in elderly patients. Blood. 2004;103:2908–13.
pubmed: 15070662
Willemze R, Suciu S, Meloni G, et al. High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: results of the EORTC-GIMEMA AML-12 trial. J Clin Oncol. 2014;32:219–28.
pubmed: 24297940
Morra E, Barosi G, Bosi A, et al. Clinical management of primary non-acute promyelocytic leukemia acute myeloid leukemia: practice Guidelines by the Italian Society of Hematology, the Italian Society of Experimental Hematology, and the Italian Group for Bone Marrow Transplantation. Haematologica. 2009;94:102–12.
pubmed: 19001282
O’Donnell MR, Tallman MS, Abboud CN, et al. Acute myeloid leukemia, version 2.2013. J Natl Compr Canc Netw. 2013;11:1047–55.
pubmed: 24029121
pmcid: 4161234
Olivieri A, Capelli D, Troiani E, et al. A new intensive induction schedule, including high-dose idarubicin, high-dose aracytin and amifostine, in older AML patients: feasibility and long-term results in 42 patients. Exp Hematol. 2007;35:1074–82.
pubmed: 17588476
Mandelli F, Vignetti M, Suciu S, et al. Daunorubicin versus mitoxantrone versus idarubicin as induction and consolidation chemotherapy for adults with acute myeloid leukemia: the EORTC and GIMEMA Groups Study AML-10. J Clin Oncol. 2009;27:5397–403.
pubmed: 19826132
pmcid: 2773224
Pautas C, Merabet F, Thomas X, et al. Randomized study of intensified anthracycline doses for induction and recombinant interleukin-2 for maintenance in patients with acute myeloid leukemia age 50 to 70 years: results of the ALFA-9801 study. J Clin Oncol. 2010;28:808–14.
pubmed: 20048183
Etienne A, Esterni B, Charbonnier A, et al. Comorbidity is an independent predictor of complete remission in elderly patients receiving induction chemotherapy for acute myeloid leukemia. Cancer. 2007;109:1376–83.
pubmed: 17326052
Repetto L, Fratino L, Audisio RA, et al. Comprehensive geriatric assessment adds information to Eastern Cooperative Oncology Group performance status in elderly cancer patients: an Italian Group for Geriatric Oncology study. J Clin Oncol. 2002;20:494–502.
pubmed: 11786579
Flood KL, Carrll MB, Le CV, et al. Geriatric sindrome in elderly patients admitted to an oncology-acute care for elders unit. J Clin Oncol. 2006;24:2298–303.
pubmed: 16710027
Balducci L, Extermann M. Management of cancer in the older person: a practical approach. Oncologist. 2000;5:224–37.
pubmed: 10884501
Olivieri A, Gini G, Bocci C, et al. Tailored therapy in an unselected population of 91 elderly patients with DLBCL prospectively evaluated using a simplified CGA. Oncologist. 2012;17:663–72.
pubmed: 22531362
pmcid: 3360906
Slovak ML, Kopecky KJ, Wolman SR, et al. Cytogenetic correlation with disease status and treatment outcome in advanced stage leukemia post bone marrow transplantation: a Southwest Oncology Group study (SWOG-8612). Leuk Res. 1995;19:381–8.
pubmed: 7596150
Capelli D, Chiarucci M, Poloni A, et al. Mobilization-driven postconsolidation therapy in elderly patients with acute myeloid leukemia: feasibility and efficacy of autologous stem cell transplantation versus low-dose gemtuzumab ozogamicin. Biol Blood Marrow Transplant. 2014;20:1399–406.
pubmed: 24880020
Cheson BD, Cassileth PA, Head DR, et al. Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia. J Clin Oncol. 1990;8:813–9.
pubmed: 2185339
Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989;10:1–10.
pubmed: 2702835
pmcid: 2702835
Amadori S, Suciu S, Jehn U, et al. Use of glycosylated recombinant human G-CSF (lenograstim) during and/or after induction chemotherapy in patients 61 years of age and older with acute myeloid leukemia: final results of AML-13, a randomized phase-3 study. Blood. 2005;106:27–34.
pubmed: 15761020
pmcid: 1895135
Rowe JM, Kim HT, Cassileth PA, et al. Adult patients with acute myeloid leukemia who achieve complete remission after 1 or 2 cycles of induction have a similar prognosis: a report on 1980 patients registered to 6 studies conducted by the Eastern Cooperative Oncology Group. Cancer. 2010;116:5012–21.
pubmed: 20629023
pmcid: 3566633
Appelbaum FR, Kopecky KJ. Long-term survival after chemotherapy for acute myeloid leukemia: the experience of the Southwest Oncology Group. Cancer. 1997;80:2199–204.
pubmed: 9395034
Malfuson JV, Etienne A, Turlure P, et al. Risk factors and decision criteria for intensive chemotherapy in older patients with acute myeloid leukemia. Haematologica. 2008;93:1806–13.
pubmed: 18838471
Sorror ML, Sandmaier BM, Storer BE, et al. Comorbidity and disease status based risk stratification of outcomes among patients with acute myeloid leukemia or myelodysplasia receiving allogeneic hematopoietic cell transplantation. J Clin Oncol. 2007;25:4246–54.
pubmed: 17724349
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–65.
Wedding U, Röhrig B, Klippstein A, et al. Impairment in functional status and survival in patients with acute myeloid leukaemia. J Cancer Res Clin Oncol. 2006;132:665–71.
pubmed: 16821071
Weiss MA, Aliff TB, Tallman MS, et al. A single, high dose of idarubicin combined with cytarabine as induction therapy for adult patients with recurrent or refractory acute lymphoblastic leukemia. Cancer. 2002;95:581–7.
pubmed: 12209751
Poloni A, Capelli D, Trappolini S, et al. Low-dose gemtuzumab-ozogamicin as post-consolidation therapy in elderly patients with acute myeloid leukaemia: a pilot study. Br J Haematol. 2010;150:119–21.
pubmed: 20377587
Capelli D, Santini G, De Souza C, et al. Amifostine can reduce mucosal damage after high-dose melphalan conditioning for peripheral blood progenitor cell autotransplant: a retrospective study. Br J Haematol. 2000;110:300–7.
pubmed: 10971385
Olivieri A, Capelli D, Montanari M, et al. Very low toxicity and good quality of life in 48 elderly patients autotransplanted for hematological malignancies: a single center experience. Bone Marrow Transplant. 2001;27:1189–95.
pubmed: 11551030
Döhner H, Estey EH, Amadori S, European LeukemiaNet, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115:453–74.
pubmed: 19880497
Lowenthal RM, Bradstock KF, Matthews JP, et al. A phase I/II study of intensive dose escalation of cytarabine in combination with idarubicin and etoposide in induction and consolidation treatment of adult acute myeloid leukemia. Australian Leukemia Study Group. Leuk Lymphoma. 1999;34:501–10.
pubmed: 10492073
Bradstock KF, Matthews JP, Lowenthal RM, et al. A randomized trial of high-versus conventional-dose cytarabine in consolidation chemotherapy for adult de novo acute myeloid leukemia in first remission after induction therapy containing high-dose cytarabine. Blood. 2005;105:481–8.
pubmed: 15213095
Appelbaum FR, Gundacker H, Head DR, et al. Age and acute myeloid leukemia. Blood. 2006;107:3481–5.
pubmed: 16455952
pmcid: 1895766
Castaigne S, Pautas C, Terré C, et al. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012;379:1508–16.
pubmed: 22482940
Arellano M, Winton E, Pan L, et al. High-dose cytarabine induction is well tolerated and active in patients with de novo acute myeloid leukemia older than 60 years. Cancer. 2012;118:428–33.
pubmed: 21717443
Clavio M, Vignolo L, Albarello A, et al. Adding low-dose gemtuzumab ozogamicin to fludarabine, Ara-C and idarubicin (MY-FLAI) may improve disease-free and overall survival in elderly patients with non-M3 acute myeloid leukaemia: results of a prospective, pilot, multi-centre trial and comparison with a historical cohort of patients. Br J Haematol. 2007;138:186–95.
pubmed: 17593025
Candoni A, Martinelli G, Toffoletti E, et al. Gemtuzumab-ozogamicin in combination with fludarabine, cytarabine, idarubicin (FLAI-GO) as induction therapy in CD33-positive AML patients younger than 65 years. Leuk Res. 2008;32:1800–8.
pubmed: 18621416
Ferrara F, D’Arco AM, De Simone M, et al. Fludarabine and cytarabine as continuous sequential infusion for elderly patients with acute myeloid leukemia. Haematologica. 2005;90:776–84.
pubmed: 15951290
Kantarjian H, Ravandi F, O’Brien S, et al. Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia. Blood. 2010;116:4422–9.
pubmed: 20668231
pmcid: 4081299
Burnett AK, Russell NH, Hunter AE, et al. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood. 2013;122:1384–94.
pubmed: 23838349
Faderl S, Wetzler M, Rizzieri D, et al. Clofarabine plus cytarabine compared with cytarabine alone in older patients with relapsed or refractory acute myelogenous leukemia: results from the CLASSIC I Trial. J Clin Oncol. 2012;30:2492–9.
pubmed: 22585697
pmcid: 4874149
Dombret H, Seymour JF, Butrym A, 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.
pubmed: 25987659
pmcid: 4504945
Kantarjian HM, Thomas XG, Dmoszynska A, et al, Arthur C. 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.
pubmed: 22689805
pmcid: 4874148
Thomas X, Suciu S, Rio B, et al. Autologous stem cell transplantation after complete remission and first consolidation in acute myeloid leukemia patients aged 61-70 years: results of the prospective EORTC–GIMEMA AML–13 study. Haematologica. 2007;92:389–96.
pubmed: 17339189
Oriol A, Ribera JM, Esteve J, et al. Feasibility and results of autologous stem cell transplantation in de novo acute myeloid leukemia in patients over 60 years old. Results of the CETLAM AML-99 protocol. Haematologica. 2004;89:791–800.
pubmed: 15257930
Scholl S, Theuer C, Scheble V, et al. Clinical impact of nucleophosmin mutations and Flt3 internal tandem duplications in patients older than 60 yr with acute myeloid leukaemia. Eur J Haematol. 2008;80:208–15.
pubmed: 18081718
Röllig C, Bornhäuser M, Thiede C, et al. Long-term prognosis of acute myeloid leukemia according to the new genetic risk classification of the European LeukemiaNet recommendations: evaluation of the proposed reporting system. Blood. 2010;115:453–74.
Sorror M, Giralt S, Sandmaier B, et al. Hematopoietic cell transplantation-specific comorbidity index as an outcome predictor for patients with acute myeloid leukemia in first remission: combined FHCRC and MDACC experiences. Blood. 2007;110:4606–13.
pubmed: 17873123
pmcid: 2234788
Löwenberg B, Beck J, Graux C, et al. Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more: results of a multicenter phase 3 study. Blood. 2010;115:2586–91.
pubmed: 20103782
Itzykson R, Gardin C, Pautas C, et al. Impact of post-remission therapy in patients aged 65-70 years with de novo acute myeloid leukemia: a comparison of two concomitant randomized ALFA trials with overlapping age inclusion criteria. Haematologica. 2011;96:837–44.
pubmed: 21459791
pmcid: 3105645