Forsaken Pharmaceutical: Glasdegib in Acute Myeloid Leukemia and Myeloid Diseases.

Advancements in the understanding of the pathogenesis of acute myeloid leukemia (AML) have led to the introduction and approval of a number of novel drugs in AML. Glasdegib, an oral hedgehog pathway inhibitor, was approved in 2018 in combination with low-dose cytarabine for the treatment of newly diagnosed AML in patients unfit for intensive chemotherapy. In this review, we discuss the preclinical rationale for glasdegib, important clinical trials that led to glasdegib's approval, and future trials of glasdegib in AML and other myeloid diseases. Notably, 2 large randomized, placebo-controlled phase 3 trials (AML BRIGHT 1019) are currently recruiting patients with newly diagnosed AML to evaluate glasdegib in combination with intensive chemotherapy or azacitidine, depending on the patient's ability to tolerate induction chemotherapy. While glasdegib and low-dose cytarabine have been eclipsed by venetoclax and hypomethylating agent combinations for newly diagnosed AML in the United States, we discuss other areas where glasdegib may still have an opportunity to improve outcomes in this devastating disease.

Management of chemotherapy-induced neutropenic fever.

Fever occurs at high rates in patients with chemotherapy-induced neutropenia and is considered an oncologic emergency. Numerous algorithms have been developed to guide treatment decisions. Prompt care and the initiation of empiric antibiotic therapy are critically important universal aspects of these treatment-decision schemata. Fever may be the only sign of infection, as in patients with cancer who are undergoing chemotherapy, the immune response is attenuated. In the majority of cases, no etiology for neutropenic fever is uncovered; nonetheless, a thorough workup is essential. The workup allows practitioners to risk stratify patients as being at low or high risk for infectious complications so that appropriate care can be administered. Although it is important to note that there are management algorithms to follow, every patient may present and respond differently. We generally start with broad-spectrum monotherapy for Gram-negative bacteria and then consider whether Gram-positive or antifungal coverage is necessary based on the clinical picture, including factors such as duration and degree of neutropenia. It is important for all practitioners to understand how to care for patients with neutropenic fever because it is a common and treatable condition.