267
Views
0
CrossRef citations to date
0
Altmetric
Review

Emerging therapies for AML with myelodysplasia-related changes: slowly but surely moving the needle

ORCID Icon & ORCID Icon
Pages 245-257 | Received 20 Apr 2021, Accepted 29 Jun 2021, Published online: 06 Jul 2021

References

  • Surveillance, Epidemiology, and End Results Program. Cancer stat facts- acute myeloid leukemia. National Cancer Institute, [cited 2021 Feb 18]. Available from: https://seer.cancer.gov/statfacts/html/amyl.html
  • Mrózek K, Marcucci G, Nicolet D, et al. Prognostic significance of the European leukemia net standardized system for reporting cytogenetic and molecular alterations in adults with acute myeloid leukemia. J Clin Oncol. 2012;30(36):4515–4523.
  • Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an expert panel. Blood. 2017;129(4):424–447.
  • Lindsley RC, Mar BG, Mazzola E, et al. Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood. 2015;125(9):1367–1376.
  • Baer C, Walter W, Stengel A, et al. Molecular classification of AML-MRC reveals a distinct profile and identifies MRC-like patients with poor overall survival. Blood. 2019;134(Supplement 1):2735.
  • Chiche E, Rahmé R, Bertoli S, et al. Real-life experience with CPX-351 and impact on the outcome of high-risk AML patients: a multicentric French cohort. Blood Adv. 2021;5(1): 176–184.
  • Devillier R, Gelsi-Boyer V, Brecqueville M, et al. Acute myeloid leukemia with myelodysplasia-related changes are characterized by a specific molecular pattern with high frequency of ASXL1 mutations. Am J Hematol. 2012;87(7):659–662.
  • Montalban-Bravo G, Kanagal-Shamanna R, Class CA, et al. Outcomes of acute myeloid leukemia with myelodysplasia related changes depend on diagnostic criteria and therapy. Am J Hematol. 2020;95(6):612–622.
  • Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114(5):937–951.
  • Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–2405.
  • Surveillance, Epidemiology, and End Results Program. Hematopoietic and lymphoid neoplasm database. National Cancer Institute, [cited 2021 Feb 18]. Available from: https://seer.cancer.gov/seertools/hemelymph/51f6cf58e3e27c3994bd53ae
  • Granfeldt Østgård LS, Medeiros BC, Sengeløv H, et al. Epidemiology and clinical significance of secondary and therapy-related acute myeloid leukemia: a national population-based cohort study. J Clin Oncol. 2015;33(31):3641–3649.
  • Jiang G, Capo-Chichi JM, Liu A, et al. Acute myeloid leukemia with myelodysplasia-related changes diagnosed with multilineage dysplasia alone demonstrates a superior clinical outcome. Hum Pathol. 2020;104:117–126.
  • Xu XQ, Wang JM, Gao L, et al. Characteristics of acute myeloid leukemia with myelodysplasia-related changes: a retrospective analysis in a cohort of Chinese patients. Am J Hematol. 2014;89(9):874–881.
  • Yates JW, Wallace HJ Jr, Ellison RR, et al. Cytosine arabinoside (NSC-63878) and daunorubicin (NSC-83142) therapy in acute nonlymphocytic leukemia. Cancer Chemother Rep. 1973;57(4):485–488.
  • Burnett AK. Treatment of acute myeloid leukemia: are we making progress? Hematology Am Soc Hematol Educ Program. 2012;2012(1):1–6.
  • Stone RM, Mazzola E, Neuberg D, et al. Phase III open-label randomized study of cytarabine in combination with amonafide L-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia. J Clin Oncol. 2015;33(11): 1252–1257.
  • Fernandez HF, Sun Z, Yao X, et al. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009;361(13):1249–1259.
  • Luskin MR, Lee JW, Fernandez HF, et al. Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups. Blood. 2016;127(12):1551–1558.
  • 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(9825):1508–1516.
  • Lambert J, Pautas C, Terré C, et al. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica. 2019;104(1):113–119.
  • Tardi P, Johnstone S, Harasym N, et al. In vivo maintenance of synergistic cytarabine: daunorubicinratios greatly enhances therapeutic efficacy. Leuk Res. 2009;33(1):129–139.
  • Mayer LD, Tardi P, Louie AC. CPX-351: a nanoscale liposomal co-formulation of daunorubicin and cytarabine with unique biodistribution and tumor cell uptake properties. Int J Nanomedicine. 2019;14:3819–3830.
  • Feldman EJ, Lancet JE, Kolitz JE, et al. First-in-man study of CPX-351: a liposomal carrier containing cytarabine and daunorubicin in a fixed 5:1 molar ratio for the treatment of relapsed and refractory acute myeloid leukemia. J Clin Oncol. 2011;29(8):979–985.
  • Feldman EJ, Kolitz JE, Trang JM, et al. Pharmacokinetics of CPX-351; a nano-scale liposomal fixed molar ratio formulation of cytarabine: daunorubicin, in patients with advanced leukemia. Leuk Res. 2012;36(10):1283–1289.
  • Lancet JE, Cortes JE, Hogge DE, et al. Phase 2 trial of CPX-351, a fixed 5:1 molar ratio of cytarabine/daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML. Blood. 2014;123(21): 3239–3246.
  • Lancet JE, Uy GL, Cortes JE, et al. CPX-351 (cytarabine and daunorubicin) liposome injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018;36(26): 2684–2692.
  • Lancet JE, Uy GL, Newell LF, et al. Five-year final results of a phase III study of CPX-351 versus 7+3 in older adults with newly diagnosed high-risk/secondary AML. J Clin Oncol. 2020;38(Supplement 15):7510.
  • Lin TL, Rizzieri DA, Ryan DH, et al. Older adults with newly diagnosed high-risk/secondary AML who achieved remission with CPX-351: phase 3 post hoc analyses. Blood Adv. 2021;5(6): 1719–1728.
  • Lindsley RC, Gibson CJ, Murdock HM, et al. Genetic characteristics and outcomes by mutation status in a phase 3 study of CPX-351 versus 7+3 in older adults with newly diagnosed, high-risk/secondary acute myeloid leukemia (AML). Blood. 2019;134(Supplement1): 15.
  • Krauss AC, Gao X, Li L, et al. FDA approval summary: (daunorubicin and cytarabine) liposome for injection for the treatment of adults with high-risk acute myeloid leukemia. Clin Cancer Res. 2019;25(9):2685–2690.
  • U.S. Food and Drug Administration. Drug Approval Package: VYXEOS (daunorubicin and cytarabine), Approval Letter, [cited 2021 Feb 23]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209401Orig1s000Approv.pdf
  • Przespolewski AC, Talati C, Fazal S, et al. Safety and efficacy of CPX-351 in younger patients <60 years old with secondary acute myeloid leukemia: an updated analysis. J Clin Oncol. 2019;37:e18530.
  • Lee D, Asghari HH, Deutsch YE, et al. CPX-351 as induction chemotherapy yields similar responses and survival outcomes in younger patients (<60 years old) compared to older patients (≥60 years old) with acute myeloid leukemia. Blood. 2019;134(Supplement 1):3894.
  • 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):291–299.
  • DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383(7): 617–629.
  • Wei AH, Montesinos P, Ivanov V, et al. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood. 2020;135(24): 2137–2145.
  • Burnett AK, Milligan D, Prentice AG, et al. A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment. Cancer. 2007;109(6):1114–1124.
  • Stresemann C, Lyko F. Modes of action of the DNA methyltransferase inhibitors azacytidine and decitabine. Int J Cancer. 2008;123(1):8–13.
  • Silverman LR, Demakos EP, Peterson BL, et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol. 2002;20(10):2429–2440.
  • Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10(3):223–232.
  • Kantarjian H, Issa JP, Rosenfeld CS, et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer. 2006;106(8):1794–1803.
  • 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):291–299.
  • Seymour JF, Döhner H, Butrym A, et al. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017;17(1):852.
  • 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):2670–2677.
  • Konopleva M, Letai A. BCL-2 inhibition in AML: an unexpected bonus? Blood. 2018;132(10):1007–1012.
  • Bogenberger JM, Delman D, Hansen N, et al. Ex vivo activity of BCL-2 family inhibitors ABT-199 and ABT-737 combined with 5-azacytidine in myeloid malignancies. Leuk Lymphoma. 2015;56(1):226–229.
  • DiNardo CD, Pratz K, Pullarkat V, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019;133(1):7–17.
  • Pollyea DA, Pratz K, Letai A, et al. Venetoclax with azacitidine or decitabine in patients with newly diagnosed acute myeloid leukemia: long term follow-up from a phase 1b study. Am J Hematol. 2021;96(2):208–217.
  • Salhotra A, Aribi A, Ngo D, et al. Outcome of secondary acute myeloid leukemia treated with hypomethylating agent plus venetoclax (HMA-Ven) or liposomal daunorubicin-cytarabine (CPX-351). Am J Hematol. 2021 Mar 14;96(6): Epub ahead of print. PMID: 33719090. DOI:https://doi.org/10.1002/ajh.26157.
  • Fukushima N, Minami Y, Kakiuchi S, et al. Small-molecule Hedgehog inhibitor attenuates the leukemia-initiation potential of acute myeloid leukemia cells. Cancer Sci. 2016;107(10):1422–1429.
  • 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): 379–389.
  • Heuser M, Smith BD, Fiedler W, et al. Clinical benefit of glasdegib plus low-dose cytarabine in patients with de novo and secondary acute myeloid leukemia: long-term analysis of a phase II randomized trial. Ann Hematol. 2021 Mar 19. Epub ahead of print. PMID: 33740113. DOI:https://doi.org/10.1007/s00277-021-04465-4.
  • Norsworthy KJ, By K, Subramaniam S, et al. FDA approval summary: glasdegib for newly diagnosed acute myeloid leukemia. Clin Cancer Res. 2019;25(20):6021–6025.
  • Borate U, Smith BD, Gore S, et al. Phase IB study of glasdegib (PF-04449913) in combination with azacitidine in patients with higher risk myelodysplastic syndrome, oligoblastic acute myeloid leukemia, or chronic myelomonocytic leukemia. Haematologica. 2016;101(Supplement 1):73–74.
  • Savona MR, Pollyea DA, Stock W, et al. Phase Ib study of glasdegib, a hedgehog pathway inhibitor, in combination with standard chemotherapy in patients with AML or high-risk MDS. Clin Cancer Res. 2018;24(10):2294–2303.
  • Cortes JE, Smith BD, Wang ES, et al. Glasdegib in combination with cytarabine and daunorubicin in patients with AML or high-risk MDS: phase 2 study results. Am J Hematol. 2018;93(11):1301–1310.
  • Cortes JE, Dombret H, Merchant A, et al. Glasdegib plus intensive/nonintensive chemotherapy in untreated acute myeloid leukemia: BRIGHT AML 1019 Phase III trials. Future Oncol. 2019;15(31):3531–3545.
  • Zeidner JF, Foster MC. Immunomodulatory drugs: iMiDs in acute myeloid leukemia (AML). Curr Drug Targets. 2017;18(3):304–314.
  • Ustun C, Miller JS, Munn DH, et al. Regulatory T cells in acute myelogenous leukemia: is it time for immunomodulation? Blood. 2011;118(19):5084–5095.
  • Szczepanski MJ, Szajnik M, Czystowska M, et al. Increased frequency and suppression by regulatory T cells in patients with acute myelogenous leukemia. Clin Cancer Res. 2009;15(10):3325–3332.
  • Knaus HA, Berglund S, Hackl H, et al. Signatures of CD8+ T cell dysfunction in AML patients and their reversibility with response to chemotherapy. JCI Insight. 2018;3(21):e120974.
  • Zhou Q, Bucher C, Munger ME, et al. Depletion of endogenous tumor-associated regulatory T cells improves the efficacy of adoptive cytotoxic T-cell immunotherapy in murine acute myeloid leukemia. Blood. 2009;114(18):3793–3802.
  • Zeidner JF, Knaus HA, Zeidan AM, et al. Immunomodulation with pomalidomide at early lymphocyte recovery after induction chemotherapy in newly diagnosed AML and high-risk MDS. Leukemia. 2020;34(6):1563–1576.
  • Norsworthy KJ, DeZern AE, Tsai HL, et al. Timed sequential therapy for acute myelogenous leukemia: results of a retrospective study of 301 patients and review of the literature. Leuk Res. 2017;61:25–32.
  • Swords RT, Kelly KR, Smith PG, et al. Inhibition of NEDD8-activating enzyme: a novel approach for the treatment of acute myeloid leukemia. Blood. 2010;115(18):3796–3800.
  • Fathi AT. Pevonedistat, a new partner for 5-azacitidine. Blood. 2018;131(13):1391–1392.
  • Swords RT, Coutre S, Maris MB, et al. Pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, combined with azacitidine in patients with AML. Blood. 2018;131(13):1415–1424.
  • Becker PS, Medeiros BC, Stein AS, et al. G-CSF priming, clofarabine, and high dose cytarabine (GCLAC) for upfront treatment of acute myeloid leukemia, advanced myelodysplastic syndrome or advanced myeloproliferative neoplasm. Am J Hematol. 2015;90(4):295–300.
  • Jaglal MV, Duong VH, Bello CM, et al. Cladribine, cytarabine, filgrastim, and mitoxantrone (CLAG-M) compared to standard induction in acute myeloid leukemia from myelodysplastic syndrome after azanucleoside failure. Leuk Res. 2014;38(4):443–446.
  • Talati C, Goldberg AD, Przespolewski A, et al. Comparison of induction strategies and responses for acute myeloid leukemia patients after resistance to hypomethylating agents for antecedent myeloid malignancy. Leuk Res. 2020;93:106367.
  • Chao MP, Takimoto CH, Feng DD, et al. Therapeutic targeting of the macrophage immune checkpoint CD47 in myeloid malignancies. Front Oncol. 2020;9:1380.
  • Sallman DA, Asch AS, Al Malki MM, et al. The first-in-class anti-CD47 antibody magrolimab (5F9) in combination with azacitidine is effective in MDS and AML patients: ongoing phase 1b results. Blood. 2019;134(Supplement 1):569.
  • Sallman DA, Asch AS, Kambhampati S, et al. The first-in-class anti-CD47 antibody magrolimab combined with azacitidine is well-tolerated and effective in AML patients: phase 1b results. Blood. 2020. Abstract 330.
  • Gardin C, Pautas C, Fournier E, et al. Added prognostic value of secondary AML-like gene mutations in ELN intermediate-risk older AML: ALFA-1200 study results. Blood Adv. 2020;4(9):1942–1949.
  • Stahl M, Menghrajani K, Derkach A, et al. Clinical and molecular predictors of response and survival following venetoclax therapy in relapsed/refractory AML. Blood Adv. 2021;5(5):1552–1564.
  • Nechiporuk T, Kurtz SE, Nikolova O, et al. The TP53 apoptotic network is a primary mediator of resistance to BCL2 inhibition in AML cells. Cancer Discov. 2019;9(7):910–925.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.