New approaches in treatment of acute myeloid leukemia

New approaches in treatment of acute myeloid leukemia

Historically acute myeloid leukemia (AML) treatment was limited to standard intensive induction chemotherapy with a combination of cytarabine and anthracycline for fit patients and non-intensive strategies with hypomethylating agent (HMA) or low dose cytarabine (LDAC). Allogeneic stem cell transplantation has also become an important treatment option that prolongs survival in selected patients. Over the last years with a better understanding of genomic and molecular pathogenesis of the disease, new treatment options have emerged with the contribution of translational studies. Especially less intensive frontline options have expanded. The combination of targeted therapies and standard therapies has helped to overcome treatment resistance and led to prolong survival. In this article, new approaches and especially targeted agents in the treatment of AML are discussed.

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  • 1. Papaemmanuil E, Gerstung M, Bullinger M, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374:2209- 21.
  • 2. Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129:424-47.
  • 3. Fernandez HF, Sun Z, Yao X, et al. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009;361:1249-59.
  • 4. Lowenberg 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.
  • 5. Ravandi F, Estey E, Jones D, et al. Effective treatment of acute promyelocytic leukemia with all-trans retinoic acid, arsenic trioxide, and gemtuzumab ozogamycin. J Clin Oncol. 2009;27:504-10.
  • 6. DiNardo CD, Wei AH. How I treat acute myeloid leukemia in the era of new drugs. Blood. 2020;135;85-96.
  • 7. Liu H. Emerging agents and regimens for AML. J Hematol Oncol. 2021;14:49.
  • 8. Kantajian HM, Kadia TM, DiNardo CD, et al. Acute myeloid leukemia treament and research outlook for 2021 and the MD Anderson approach. Cancer. 2021;86:1186-1207.
  • 9. Kern W, Estey EH. High-dose cytosine arabinoside in the treatment of acute myeloid leukemia: review of three randomized trails. Cancer. 2006;107:116-24.
  • 10. Burnett AK, Russel NH, Hills RK, et al. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of medical research council AML15 trial. J Clin Oncol. 2013;31:3360-8.
  • 11. Mayer RJ, Davis RB, Schiffer CA, et al. Intensive postremission chemotehrapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B. N Engl J Med. 1994;331:896-903.
  • 12. Candoni A, Papayannidis C, Martinelli G, et al. Flai (fludarabine, cytarabine, idarubicin) plus low-dose gemtuzumab ozogamicin as induction therapy in CD33-positive AML: final results and long term outcome of a phase II multicenter clinical trial. Am J Hematol. 2018;93:655-63.
  • 13. Holowiecki J, Grosicki S, Robak T, et al. Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia. Multicenter, phase III study. Leukemia. 2004;18:989-97.
  • 14. Hills RK, Castaigne S, Appelbaum FR, et al. Addition of gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukemia: a meta analysis of individual pateint data from randomised controlled trails. Lancet Oncol. 2014;15:986-96.
  • 15. Borthakur GM, Cortes JE, Ravandi F, et al. Fludarabine, Cytarabine, G-CSF and Gemtuzumab Ozogamicin (FLAG-GO) regimen results in better molecular response and relapse-free survival in core binding factor acute myeloid leukemia than FLAG and Idarubicin (FLAG-Ida). Blood. 2019;134:290.
  • 16. Campos L, Rouault JP, Sabido O, et al. High expression of bcl-2 protein in acute myeloid leukemia cells is associated with poor response to chenotherapy. Blood. 1993;81:3091-6.
  • 17. Pan R, Hodgal LJ, Benito JM, et al. Selective BCL-2 inhibitor by ABT199 causes on-target cell death in acute myeloid leukemia. Cancer Discov. 2014;4:362-75.
  • 18. 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;6:1106-17.
  • 19. 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;133:7-17.
  • 20. Wei AH, Strickland SA Jr, Hou JZ, et al. Venetoclax combined with lowdose cytarabine for previously untreated patients with acute myeloid leukemia: results form a phase Ib/II study. J Clin Oncol. 2019;37:1277-84.
  • 21. DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in perviously untreated acute myeloid leukemia. N Engl J Med. 2020;383:617- 29.
  • 22. Wei AH, Montesinos P, Ivanov V, et al. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-conrolled trial. Blood. 2020;135:2137-45.
  • 23. DiNardo CD, Maiti A, Rausch CR, et al. 10-day decitabine with venetoclax for newly diagnosed acute intensive chemotehrapy ineligible, and relapsed or refractory myeloid leukemia: a single-centre, phase 2 trial. Lancet Haematol. 2020;7:e724-e736.
  • 24. Lachowiez C, Konopleva M, Kadia T, et al. Interim analysis of the phase 1b/2 study of the BCL-2 inhibitor venetoclax in combination with standard intensive AML induction/consolidation therapy with FLAG-IDA in patients with newly diagnosed or relapsed/refractory AML. Blood. 2020;136:332.
  • 25. Chua CC, Roberts AW, Reynolds J, et al. Chemotherapy and venetoclax in elderly acute myeloid leukemia trail (CAVEAT): a phase Ib dose escalation study of venetoclax combined with modified intensive chemotherapy. J Clin Oncol. 2020;35:3506-17.
  • 26. Kadia TM, Garcia-Manero G, Yilmaz M, et al. Venetoclax (Ven) added to intensive chemo with cladribine, idarubicin, and AraC (CLIA) achieves high rates of durable (MRD) in pts with newly diagnosed acute myeloid leukemia (AML). J Clin Oncol. 2020;38:7539.
  • 27. Kadia TM, Borthakur G, Pemmaraju N, et al. Phase II study of venetoclax added to cladribine + low dose AraC (LDAC) alternating with 5-azacytidine demostrates high rates of minimal residual disease (MRD) negative complete remissions (CR) and excellent tolerability in older patients with newly diagnosed acute myeloid leukemia (AML) ). Blood. 2020;136:17-19.
  • 28. Kadia TM, Borthakur G, Takahashi K, et al. Phase II study of CPX-351 plus venetoclax in patients with acute myeloid leukemia (AML). Blood. 2020;136:20-2.
  • 29. Stein E, DiNardo C, Pollyea D, et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood. 2017;130:722-3.
  • 30. 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;378:2386-98.
  • 31. DiNardo C, Scuh A, Stein E. Enasidenib plus azacytidine significantly improves complete remission and overall response compared with azacitidine alone in patients with newly diagnosed acute myeloid leukemia (AML) with isocitrate dehydrogenase 2 (IDH2) mutations: interim phase II results from an ongoing , randomized study. Blood. 2019;134:643.
  • 32. Stein EM, DiNardo CD, Fathi AT, et al. Ivosidenib or enasidenib combined with intensive chemotherapy in patients with newly diagnosed AML: a phase 1 study. Blood. 2021;137:1792-1803.
  • 33. Frisch A, Rowe JM, Ofran Y. How we treat older patients with acute myeloid leukaemia. Br J Haematol. 2020;191:682-91.
  • 34. Perl AE, Martinelli G, Cortes JE, et al. Gilteritinib or chmeoteherapy for relapsed or refractory FLT-3mutated AML. N Engl J Med. 2019;381:1728-40.
  • 35. Cortes JE, Tallman MS, Schiller GJ, et al. Phase 2b study of 2 dosing regimens of quizartinib monotherapy in FLT3-ITD-mutated, relapsed or refractory AML. Blood. 2018;132:598-607.
  • 36. Stone RM, Mandrekar SJ, Sanford BL, et al. Midostaurin plus chemotherapy for acute myelody leukemia with a FLT3 mutation. N Engl J Med. 2017;377:454-64.
  • 37. Pratz K, Cherry M, Altman J, et al. A Phase 1 study of gilteritinib in combination with induction and consolidation chemotherapy in patients with newly diagnosed AML: final results. Blood. 2020;21:1201-12.
  • 38. Buchert A, Bug G, Fritz LV, Finke J, et al. Sorafenib maintanence after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with FLT3-internal tandem duplication mutation (SORMAIN). J Clin Oncol. 2020;38:2993-3002.
  • 39. Lancet JE, Uy GL, Cortes JE, et al. CPX351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myelodi leukemia. J Clin Oncol. 2018;36:2684-92.
  • 40. Jamieson CH, Martinelli G, Papayannidis C, et al. Hedgehog pathway inhibitors: a new tehrapeutic class fort the treatemnt of acute myeloid leukemia. Blood Cancer Discov. 2020;1:134-45.
  • 41. Cortes JE, Heidel FH, Hellmann A, et al. Randomized comparizon 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.
  • 42. Sallman D, DeZern AE, Garcia-Manero G, et al. Phase 2 results of APR246 and azacytidine (AZA) in patients with TP53 mutant myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia (AML). Blood. 2019;134:676.
  • 43. Sallman D, Asch A, Kambhamptati S, et al. The first-in-class anti-CD47 antibodies magrolimab in combinatiom with azacitidine is effective in AML patients: phase 1b results. Blood. 2020;136. Abstract 330.
  • 44. Wei A, Dohner H, Pocock C, et al. Oral azacitidine maintenance therapy for acute myeloid leukemia in first remission. N Engl J Med. 2020;383:2526- 37.
  • 45. Huls G, Chitu DA, Havelange V, et al. Azacitidine maintenance after intensive chemotehrapy improves DFS in older AML patients. Blood. 2019;133:1457-64.
  • 46. Heuser M, Ofran Y, Boissel N, et al. Acute myeloid leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up. Ann Oncol. 2020;31:697-712.
Medicine Science-Cover
  • ISSN: 2147-0634
  • Yayın Aralığı: Yılda 4 Sayı
  • Başlangıç: 2012
  • Yayıncı: Effect Publishing Agency ( EPA )
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