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Novel therapies have also emerged for newly diagnosed AML in adults who are age 75\u2009years or older, or who have comorbidities that preclude the use of intensive induction chemotherapy. These include venetoclax (BCL\u20102 inhibitor) in combination with hypomethylating agents (azacitidine or decitabine) or low\u2010dose cytarabine (LDAC), and glasdegib (sonic hedgehog pathway inhibitor) in combination with LDAC. This flurry of new drug approvals has markedly altered the treatment landscape in AML and provided new opportunities, as well as new challenges for treating clinicians. This review will focus on how these drugs might shape clinical practice and the hurdles likely to be faced by new therapies seeking entry into this dynamic and rapidly changing therapeutic landscape.<\/jats:p>","DOI":"10.1002\/gcc.22750","type":"journal-article","created":{"date-parts":[[2019,3,12]],"date-time":"2019-03-12T19:51:15Z","timestamp":1552420275000},"page":"903-914","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["New drugs creating new challenges in acute myeloid leukemia"],"prefix":"10.1002","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7417-4343","authenticated-orcid":false,"given":"Ing S.","family":"Tiong","sequence":"first","affiliation":[{"name":"Department of Haematology The Alfred Hospital and Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew H.","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Haematology The Alfred Hospital and Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,11]]},"reference":[{"issue":"12","key":"e_1_2_9_2_1","first-page":"1911","article-title":"Internal tandem duplication of the flt3 gene found in acute myeloid leukemia","volume":"10","author":"Nakao M","year":"1996","journal-title":"Leukemia"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.8.2434"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa074306"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-08-733196"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2017011080"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(02)00069-7"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1614359"},{"issue":"1","key":"e_1_2_9_9_1","first-page":"467","article-title":"Prognostic impact of NPM1\/FLT3\u2010ITD genotypes from randomized patients with acute myeloid leukemia (AML) treated within the international Ratify study","volume":"130","author":"D\u00f6hner K","year":"2017","journal-title":"Blood"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-693648"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018020305"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-09-807438"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1507471"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-08-869453"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.46.4990"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25027"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells7010004"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-16-0876"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00362-9"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-10-529313"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2014.32.15_suppl.7070"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V128.22.1071.1071"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-99-117016"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-99-110975"},{"issue":"1","key":"e_1_2_9_25_1","first-page":"145","article-title":"An analysis of maintenance therapy and post\u2010Midostaurin outcomes in the international prospective randomized, placebo\u2010controlled, double\u2010blind trial (CALGB 10603\/RATIFY [Alliance]) for newly diagnosed acute myeloid leukemia (AML) patients with FLT3 mutations","volume":"130","author":"Larson RA","year":"2017","journal-title":"Blood"},{"issue":"1","key":"e_1_2_9_26_1","first-page":"323","article-title":"Sorafenib maintenance in FLT3\u2010ITD mutated acute myeloid leukemia after allogeneic stem cell transplant","volume":"102","author":"Ahmed S","year":"2017","journal-title":"Haematologica"},{"key":"e_1_2_9_27_1","doi-asserted-by":"crossref","unstructured":"BurchertA BugG FinkeJ et al. 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