Dtsch Med Wochenschr 2018; 143(18): 1297-1303
DOI: 10.1055/s-0043-121022
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© Georg Thieme Verlag KG Stuttgart · New York

Akute myeloische Leukämie bei Erwachsenen

Ein Update zu Diagnostik, Risikoklassifikation und TherapieAML in Adults – An Update on Diagnosis, Risk Classification and Therapy
Karsten Spiekermann
,
Anne-Sophie Shen
Further Information

Publication History

Publication Date:
10 September 2018 (online)

Abstract

There are several changes in the revised WHO classification for acute leukemia. The latest version of the European Leukemia Network (ELN)-risk classification defines AML with mutations in RUNX1, ASXL1 or TP53 to fall in the unfavorable risk group. Consequently, the somatic molecular genetic testing at the time of initial diagnosis should encompass these before mentioned three genes next to the already routine testing of NPM1, CEBPA and FLT3-ITD. Several new innovative substances have been developed and approved for AML therapy. The multikinase inhibitor midostaurin is a new substance in the induction therapy for patients with FLT-3 mutated AML. CPX-351 (cytarabin and daunorubicin in liposomatic formulation in a defined molar relation) is a new option for therapy associated AML and AML with myelodysplastic changes. Enasidenib is a targeting drug for relapsed or refractory AML with IDH2 mutation. Gemtuzumab, a CD33 + antibody-drug-conjugate is approved for CD33 positive cases.

Mittlerweile sind viele neuartige und zielgerichtete Substanzen in der Therapie der AML verfügbar. Durch die Fortschritte in der Molekulargenetik lassen sich zielgerichtete Therapieoptionen ableiten. Umso wichtiger sind eine präzise und vor allem rasche zyto- und molekulargenetische Charakterisierung der AML sowie die Risikobestimmung. Dieser Beitrag legt den Schwerpunkt auf Neuerungen in der Klassifikation und bei den Therapieansätzen.

 
  • Literatur

  • 1 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: 2391-2405 . doi:10.1182/blood-2016-03-643544
  • 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: 424-447 . doi:10.1182/blood-2016-08-733196
  • 3 Welch JS, Petti AA, Miler CA. et al. TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes. N Engl J Med 2016; 375: 2023-2036 . doi:10.1056/NEJMoa1605949
  • 4 Stone RM, Mandrekar SJ, Sanford BL. et al. Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation. N Engl J Med 2017; 377: 454-464 . doi:10.1056/NEJMoa1614359
  • 5 Levis M. Midostaurin approved for FLT3-mutated AML. Blood 2017; 129: 3403-3406 . doi:10.1182/blood-2017-05-782292
  • 6 Stein EM, DiNardo CD, Pollyea DA. et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood 2017; 130 (06) 722-731 . doi:10.1182/blood-2017-04-779405
  • 7 Godwin CD, Gale RP, Walter RB. Gemtuzumab ozogamicin in acute myeloid leukemia. Leukemia 2017; 31: 1855-1868 . doi:10.1038/leu.2017.187
  • 8 Hills RK, Castaigne S, Appelbaum FR. et al. The Addition of Gemtuzumab Ozogamicin to Induction Chemotherapy in Acute Myeloid Leukaemia : An Individual Patient Data Meta-analysis of Randomised Trials in Adults. Lancet Oncol 2014; 15: 986-996 . doi:10.1016/S1470-2045(14)70281-5
  • 9 Lancet JE, Uy GL, Cortes JE. et al. Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J Clin Oncol 2016;  34: 7000 . doi:10.1200/JCO.2016.34.15_suppl.7000
  • 10 Cortes JE, Goldberg SL, Feldman EJ. et al. Phase II, multicenter, randomized trial of CPX-351 (cytarabine:daunorubicin) liposome injection versus intensive salvage therapy in adults with first relapse AML. Cancer 2015; 121: 234-242 . doi:10.1002/cncr.28974
  • 11 DiNardo CD, Pratz KW, Letai A. et al. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol 2018; 19: 216-228 . doi:10.1016/S1470-2045(18)30010-X
  • 12 Wei A, Strickland S, Roboz G. et al. Safety and efficacy of venetoclax plus low-dose cytarabine in treatment-naive patients aged ≥65 years with acute myeloid leukemia. Proceedings from the 2016 annual meeting of the American Society of Hematology (ASH). Blood 2016; 128: Abstract 102
  • 13 Röllig C, Serve H, Hüttmann 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: 1691-1699 . doi:10.1016/S1470-2045(15)00362-9
  • 14 Stein EM, Tallman MS. Emerging therapeutic drugs for AML. Blood 2016; 127 (01) 71-78 . doi:10.1182/blood-2015-07-604538
  • 15 Wei AH, Tiong IS. Midostaurin, enasidenib, CPX-351, gemtuzumab ozogamicin, and venetoclax bring new hope to AML. Blood 2017; 130: 2469-2474 . doi:10.1182/blood-2017-08-784066
  • 16 Pulte D, Jansen L, Castro FA. et al. Survival in patients with acute myeloblastic leukemia in Germany and the United States: Major differences in survival in young adults. Int J Cancer 2016; 139: 1289-1296 . doi:10.1002/ijc.30186
  • 17 Kompetenznetz akute und chronische Leukämien. https://www.kompetenznetz-leukaemie.de/content/aerzte/aml/therapieempfehlungen Stand: 25.03.2018
  • 18 Onkopedia Leitlinie AML. https://www.onkopedia.com/de/onkopedia/guidelines/akute-myeloische-leukaemie-aml Stand: 23.06.2018