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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2021

01-12-2021 | Myelodysplastic Syndrome | Review

Maintenance therapy in acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation

Authors: Li Xuan, Qifa Liu

Published in: Journal of Hematology & Oncology | Issue 1/2021

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Abstract

Relapse remains the main cause of treatment failure in acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Emerging evidence has demonstrated that AML patients might benefit from maintenance therapy post-transplantation, especially for high-risk AML patients. In this mini-review, we will summarize targeted drugs, such as hypomethylating agents, FLT3 inhibitors and isocitrate dehydrogenase inhibitors, as maintenance therapy post-transplantation in AML patients undergoing allo-HSCT.
Literature
1.
Teuffel O, Leibundgut K, Lehrnbecher T, Alonzo TA, Beyene J, Sung L. Anthracyclines during induction therapy in acute myeloid leukaemia: a systematic review and meta-analysis. Br J Haematol. 2013;161(2):192–203.PubMedCrossRef
2.
Burnett AK, Russell NH, Hills RK, et al. A randomized comparison of daunorubicin 90 mg/m2 vs 60 mg/m2 in AML induction: results from the UK NCRI AML17 trial in 1206 patients. Blood. 2015;125(25):3878–85.PubMedPubMedCentralCrossRef
3.
Piemontese S, Boumendil A, Labopin M, et al. Leukemia relapse following unmanipulated haploidentical transplantation: a risk factor analysis on behalf of the ALWP of the EBMT. J Hematol Oncol. 2019;12(1):68.PubMedPubMedCentralCrossRef
4.
Löwenberg B, Suciu S, Archimbaud E, 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.PubMedCrossRef
5.
Ferrero D, Crisà E, Marmont F, et al. Survival improvement of poor-prognosis AML/MDS patients by maintenance treatment with low-dose chemotherapy and differentiating agents. Ann Hematol. 2014;93(8):1391–400.PubMedCrossRef
6.
7.
Molica M, Breccia M, Foa R, Jabbour E, Kadia TM. Maintenance therapy in AML: The past, the present and the future. Am J Hematol. 2019;94(11):1254–65.PubMedCrossRef
8.
Lee CJ, Savani BN, Mohty M, et al. Post-remission strategies for the prevention of relapse following allogeneic hematopoietic cell transplantation for high-risk acute myeloid leukemia: expert review from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant. 2019;54(4):519–30.PubMedCrossRef
9.
10.
Schroeder T, Rautenberg C, Haas R, Germing U, Kobbe G. Hypomethylating agents for treatment and prevention of relapse after allogeneic blood stem cell transplantation. Int J Hematol. 2018;107(2):138–50.PubMedCrossRef
11.
Wang Y, Liu QF, Wu DP, et al. Impact of prophylactic/preemptive donor lymphocyte infusion and intensified conditioning for relapsed/refractory leukemia: a real-world study. Sci China Life Sci. 2020;63(10):1552–64.PubMedCrossRef
12.
Kantarjian HM, Thomas XG, Dmoszynska A, 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.PubMedPubMedCentralCrossRef
13.
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(3):291–9.PubMedPubMedCentralCrossRef
14.
Jabbour E, Giralt S, Kantarjian H, et al. Low-dose azacitidine after allogeneic stem cell transplantation for acute leukemia. Cancer. 2009;115(9):1899–905.PubMedCrossRef
15.
de Lima M, Giralt S, Thall PF, et al. Maintenance therapy with low-dose azacitidine after allogeneic hematopoietic stem cell transplantation for recurrent acute myelogenous leukemia or myelodysplastic syndrome: a dose and schedule finding study. Cancer. 2010;116(23):5420–31.PubMedCrossRef
16.
Pusic I, Choi J, Fiala MA, et al. Maintenance therapy with decitabine after allogeneic stem cell transplantation for acute myelogenous leukemia and myelodysplastic syndrome. Biol Blood Marrow Transplant. 2015;21(10):1761–9.PubMedPubMedCentralCrossRef
17.
Ma Y, Qu C, Dai H, et al. Maintenance therapy with decitabine after allogeneic hematopoietic stem cell transplantation to prevent relapse of high-risk acute myeloid leukemia. Bone Marrow Transplant. 2020;55(6):1206–8.PubMedCrossRef
18.
Maples KT, Sabo RT, McCarty JM, Toor AA, Hawks KG. Maintenance azacitidine after myeloablative allogeneic hematopoietic cell transplantation for myeloid malignancies. Leuk Lymphoma. 2018;59(12):2836–41.PubMedCrossRef
19.
Oshikawa G, Kakihana K, Saito M, et al. Post-transplant maintenance therapy with azacitidine and gemtuzumab ozogamicin for high-risk acute myeloid leukaemia. Br J Haematol. 2015;169(5):756–9.PubMedCrossRef
20.
Platzbecker U, Middeke JM, Sockel K, et al. Measurable residual disease-guided treatment with azacitidine to prevent haematological relapse in patients with myelodysplastic syndrome and acute myeloid leukaemia (RELAZA2): an open-label, multicentre, phase 2 trial. Lancet Oncol. 2018;19(12):1668–79.PubMedCrossRef
21.
de Lima M, Oran B, Champlin RE, et al. CC-486 Maintenance after stem cell transplantation in patients with acute myeloid leukemia or myelodysplastic syndromes. Biol Blood Marrow Transplant. 2018;24(10):2017–24.PubMedCrossRefPubMedCentral
22.
23.
Bazarbachi A, Bug G, Baron F, et al. Clinical practice recommendation on hematopoietic stem cell transplantation for acute myeloid leukemia patients with FLT3-internal tandem duplication: a position statement from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Haematologica. 2020;105(6):1507–16.PubMedPubMedCentralCrossRef
24.
Antar AI, Otrock ZK, Jabbour E, Mohty M, Bazarbachi A. FLT3 inhibitors in acute myeloid leukemia: ten frequently asked questions. Leukemia. 2020;34(3):682–96.PubMedCrossRef
25.
Xuan L, Wang Y, Huang F, et al. Effect of sorafenib on the outcomes of patients with FLT3-ITD acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation. Cancer. 2018;124(9):1954–63.PubMedCrossRef
26.
Rollig C, Serve H, Huttmann A, et al. Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2015;16(16):1691–9.PubMedCrossRef
27.
Xuan L, Wang Y, Chen J, et al. Sorafenib therapy is associated with improved outcomes for FMS-like tyrosine kinase 3 internal tandem duplication acute myeloid leukemia relapsing after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2019;25(8):1674–81.PubMedCrossRef
28.
29.
Chen YB, Li S, Lane AA, et al. Phase I trial of maintenance sorafenib after allogeneic hematopoietic stem cell transplantation for fms-like tyrosine kinase 3 internal tandem duplication acute myeloid leukemia. Biol Blood Marrow Transplant. 2014;20(12):2042–8.PubMedPubMedCentralCrossRef
30.
Brunner AM, Li S, Fathi AT, et al. Haematopoietic cell transplantation with and without sorafenib maintenance for patients with FLT3-ITD acute myeloid leukaemia in first complete remission. Br J Haematol. 2016;175(3):496–504.PubMedPubMedCentralCrossRef
31.
Battipaglia G, Ruggeri A, Massoud R, et al. Efficacy and feasibility of sorafenib as a maintenance agent after allogeneic hematopoietic stem cell transplantation for Fms-like tyrosine kinase 3-mutated acute myeloid leukemia. Cancer. 2017;123(15):2867–74.PubMedCrossRef
32.
Battipaglia G, Massoud R, Ahmed SO, et al. Efficacy and feasibility of sorafenib as a maintenance agent after allogeneic hematopoietic stem cell transplantation for FMS-like tyrosine kinase 3 mutated acute myeloid leukemia: an update. Clin Lymphoma Myeloma Leuk. 2019;19(8):506–8.PubMedCrossRef
33.
Bazarbachi A, Labopin M, Battipaglia G, et al. Allogeneic stem cell transplantation for FLT3-mutated acute myeloid leukemia: in vivo T-cell depletion and posttransplant sorafenib maintenance improve survival. a retrospective acute leukemia working party-European Society for Blood and Marrow Transplant Study. Clin Hematol Int. 2019;1(1):58–74.CrossRefPubMedPubMedCentral
34.
Serve H, Krug U, Wagner R, et al. Sorafenib in combination with intensive chemotherapy in elderly patients with acute myeloid leukemia: results from a randomized, placebo-controlled trial. J Clin Oncol. 2013;31(25):3110–8.PubMedCrossRef
35.
Xuan L, Wang Y, Huang F, et al. Sorafenib maintenance in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised phase 3 trial. Lancet Oncol. 2020;21(9):1201–12.PubMedCrossRef
36.
Burchert A, Bug G, Fritz LV, et al. Sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with FLT3-internal tandem duplication mutation (SORMAIN). J Clin Oncol. 2020;38(26):2993–3002.PubMedCrossRef
37.
Mathew NR, Baumgartner F, Braun L, et al. Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells. Nat Med. 2018;24(3):282–91.PubMedPubMedCentralCrossRef
38.
Metzelder SK, Schroeder T, Finck A, et al. High activity of sorafenib in FLT3-ITD-positive acute myeloid leukemia synergizes with allo-immune effects to induce sustained responses. Leukemia. 2012;26(11):2353–9.PubMedCrossRef
39.
40.
Sandmaier BM, Khaled SK, Oran B, Gammon G, Trone D, Frankfurt O. Results of a phase 1 study of quizartinib (AC220) as maintenance therapy in subjects with acute myeloid leukemia in remission following allogeneic hematopoietic cell transplantation. Blood. 2014;124(21):428.CrossRef
41.
Ganguly S, Cortes JE, Krämer A, et al. Clinical outcomes and characteristics of patients (pts) with FLT3-internal tandem duplication (FLT3-ITD)-mutated relapsed/refractory (R/R) acute myeloid leukemia (AML) undergoing hematopoietic stem cell transplant (HSCT) after quizartinib (Q) or salvage chemotherapy (SC) in the Quantum-R trial. Blood. 2019;134(Supplement_1):736.CrossRef
42.
Maziarz RT, Patnaik MM, Scott BL, et al. Radius: a phase 2 randomized trial investigating standard of care ± midostaurin after allogeneic stem cell transplant in FLT3-ITD-mutated AML. Blood. 2018;132(Supplement_1):662.CrossRef
43.
Levis MJ, Hamadani M, Logan BR, et al. BMT CTN protocol 1506: a phase 3 trial of gilteritinib as maintenance therapy after allogeneic hematopoietic stem cell transplantation in patients with FLT3-ITD+AML. Blood. 2019;134(Supplement_1):4602.CrossRef
44.
Ward PS, Patel J, Wise DR, et al. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell. 2010;17(3):225–34.PubMedPubMedCentralCrossRef
45.
DiNardo CD, Stein EM, de Botton S, et al. Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML. N Engl J Med. 2018;378(25):2386–98.PubMedCrossRef
46.
Yen K, Travins J, Wang F, et al. AG-221, a first-in-class therapy targeting acute myeloid leukemia harboring oncogenic IDH2 mutations. Cancer Discov. 2017;7(5):478–93.PubMedCrossRef
47.
Stein EM, DiNardo CD, Mims AS, et al. Ivosidenib or enasidenib combined with standard induction chemotherapy is well tolerated and active in patients with newly diagnosed AML with an IDH1 or IDH2 mutation: initial results from a phase 1 trial. Blood. 2017;130(Supplement 1):726.
48.
Konopleva M, Pollyea DA, Potluri J, et al. Efficacy and biological correlates of response in a phase II study of venetoclax monotherapy in patients with acute myelogenous leukemia. Cancer Discov. 2016;6(10):1106–17.PubMedPubMedCentralCrossRef
49.
Chua CC, Roberts AW, Reynolds J, et al. Chemotherapy and venetoclax in elderly acute myeloid leukemia trial (CAVEAT): a phase Ib dose-escalation study of venetoclax combined with modified intensive chemotherapy. J Clin Oncol. 2020;38(30):3506–17.PubMedCrossRef
50.
DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383(7):617–29.PubMedCrossRef
51.
Kent A, Pollyea DA, Winters A, Jordan CT, Smith C, Gutman JA. Venetoclax is safe and tolerable as post-transplant maintenance therapy for AML patients at high risk for relapse. Blood. 2020;136(Supplement_1):11–2.CrossRef
52.
DeAngelo DJ, Spencer A, Bhalla KN, et al. Phase Ia/II, two-arm, open-label, dose-escalation study of oral panobinostat administered via two dosing schedules in patients with advanced hematologic malignancies. Leukemia. 2013;27(8):1628–36.PubMedCrossRef
53.
Bug G, Burchert A, Wagner EM, et al. Phase I/II study of the deacetylase inhibitor panobinostat after allogeneic stem cell transplantation in patients with high-risk MDS or AML (PANOBEST trial). Leukemia. 2017;31(11):2523–5.PubMedPubMedCentralCrossRef
54.
Wellbrock J, Latuske E, Köhler J, et al. Expression of hedgehog pathway mediator GLI represents a negative prognostic marker in human acute myeloid leukemia and its inhibition exerts antileukemic effects. Clin Cancer Res. 2015;21(10):2388–98.PubMedCrossRef
55.
Cortes JE, Heidel FH, Hellmann A, 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(2):379–89.PubMedCrossRef
56.
Cortes JE, Heidel FH, Fiedler W, et al. Survival outcomes and clinical benefit in patients with acute myeloid leukemia treated with glasdegib and low-dose cytarabine according to response to therapy. J Hematol Oncol. 2020;13(1):92.PubMedPubMedCentralCrossRef
57.
58.
Yan CH, Liu DH, Liu KY, et al. Risk stratification-directed donor lymphocyte infusion could reduce relapse of standard-risk acute leukemia patients after allogeneic hematopoietic stem cell transplantation. Blood. 2012;119(14):3256–62.PubMedCrossRef
59.
Liu Y, Bewersdorf JP, Stahl M, Zeidan AM. Immunotherapy in acute myeloid leukemia and myelodysplastic syndromes: The dawn of a new era? Blood Rev. 2019;34:67–83.PubMedCrossRef
60.
Maeda T, Hosen N, Fukushima K, et al. Maintenance of complete remission after allogeneic stem cell transplantation in leukemia patients treated with Wilms tumor 1 peptide vaccine. Blood Cancer J. 2013;3(8):e130.PubMedPubMedCentralCrossRef
Metadata
Title
Maintenance therapy in acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation
Authors
Li Xuan
Qifa Liu
Publication date
01-12-2021

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