New drugs creating new challenges in acute myeloid leukemia

• Published in: Genes chromosomes & cancer Vol. 58; no. 12; pp. 903 - 914
• Main Authors: Tiong, Ing S., Wei, Andrew H.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.12.2019; Wiley Subscription Services, Inc
• Subjects: 5-aza-2'-deoxycytidine; Acute myeloid leukemia; acute myeloid leukemia review; Aminopyridines - therapeutic use; Aniline Compounds - therapeutic use; Calicheamicin; Chemotherapy; Cytarabine; Cytarabine - therapeutic use; Daunorubicin; Daunorubicin - therapeutic use; elderly AML; fms-Like Tyrosine Kinase 3 - antagonists & inhibitors; fms-Like Tyrosine Kinase 3 - genetics; Gemtuzumab - therapeutic use; Gemtuzumab ozogamicin; Glycine - analogs & derivatives; Glycine - therapeutic use; Humans; Leukemia; Leukemia, Myeloid, Acute - drug therapy; Monoclonal antibodies; Myelodysplastic syndrome; Myeloid leukemia; new challenges; Pyrazines - therapeutic use; Pyridines - therapeutic use; recent drug approvals; Staurosporine - analogs & derivatives; Staurosporine - therapeutic use; Triazines - therapeutic use; United States; United States Food and Drug Administration; United States; acute myeloid leukemia review; recent drug approvals; elderly AML; new challenges
• ISSN: 1045-2257; 1098-2264
• DOI: 10.1002/gcc.22750

The therapeutic landscape is rapidly changing, with eight new drugs approved by the Food and Drug Administration within the last 2 years, including midostaurin and gilteritinib for FLT3 mutant newly diagnosed and relapsed/refractory (R/R) acute myeloid leukemia (AML), respectively; CPX‐351 (liposomal cytarabine and daunorubicin) for therapy‐related AML and AML with myelodysplasia‐related changes; gemtuzumab ozogamicin (anti‐CD33 monoclonal antibody conjugated with calicheamicin) for newly diagnosed and R/R CD33‐positive AML; enasidenib and ivosidenib for IDH2 and IDH1 mutant R/R AML, respectively. Novel therapies have also emerged for newly diagnosed AML in adults who are age 75 years or older, or who have comorbidities that preclude the use of intensive induction chemotherapy. These include venetoclax (BCL‐2 inhibitor) in combination with hypomethylating agents (azacitidine or decitabine) or low‐dose 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.