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Glasdegib in the treatment of acute myeloid leukemia
Anna Wolska-Washer1, Tadeusz Robak1
1Department of Hematology, Medical University of Lodz, ul. Ciolkowskiego 2, 93-510 Lodz, Poland.
Abstract:
Pharmacologic inhibition of the Hedgehog pathway significantly enhanced the sensitivity of leukemic cells to cytotoxic drugs. Glasdegib (PF-04449913; DAURISMO™) is a potent and selective oral inhibitor of the Hedgehog signaling pathway with clinical activity in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), particularly in combination with chemotherapy. The results of Phase Ib/II studies evaluating safety and efficacy of glasdegib combined with chemotherapy in previously untreated patients with AML or high-risk myelodysplastic syndrome have recently been published. In the BRIGHT AML 1003 study, glasdegib in combination with low-dose cytarabine (LDAC) was well tolerated and demonstrated a significant 54% reduction in mortality compared with LDAC for AML patients. In 2018, the US FDA approved glasdegib in combination with LDAC for the treatment of newly diagnosed patients with AML who are 75 years old or older or who have co-morbidities that preclude use of intensive induction chemotherapy.
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