Leukemia Drug Gains Multiple FDA Approvals

Today, the FDA approved midostaurin (Rydapt) for the treatment of acute myeloid leukemia (AML) with FLT3 mutations (FLT3+) in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation, according to a press release.

Additionally, the FDA approved a companion diagnostic test to determine FLT3 status. The diagnostic test, LeukoStrat CDx FLT3 Mutation Assay, is to be used to test patients with AML for the FLT3 mutation prior to initiating therapy with midostaurin.

The new approval was based on positive findings from a clinical trial including 717 treatment-naïve patients with FLT3+ AML. In the study, patients were randomized to receive treatment with placebo or midostaurin 50-mg twice daily on days 8 to 21 of each cycle of induction and consolidation chemotherapy, followed by daily midostaurin for up to 12 cycles, according to the release.

The investigators found that treatment with midostaurin demonstrated a statistically significant improvement in overall survival compared with placebo.

Common adverse events included febrile neutropenia, nausea, mucositis, vomiting, headache, petechiae, musculoskeletal pain, epistaxis, device-related infection, hyperglycemia, and upper respiratory tract infection. The FDA notes that 16% of patients in both treatment groups experienced febrile neutropenia.

"The overall survival advantage for midostaurin plus chemotherapy seen in the RATIFY trial was a significant advancement for newly diagnosed AML patients with the FLT3 mutation," said Richard Stone, MD, chief of staff and director of the Adult Leukemia program at Dana-Farber Cancer Institute, and Alliance for Clinical Trials in Oncology study chair for the RATIFY trial. "The availability of midostaurin now helps to establish a new standard of care in this high-risk patient population.

The FDA also approved midostaurin for the treatment of aggressive systemic mastocytosis (SM), SM with associated hematological neoplasm, or mast cell leukemia, according to the release. This approval was based on response rate and duration in a clinical trial of midostaurin 100-mg twice daily.

The investigators discovered that 6 cycles of midostaurin resulted in confirmed complete remission plus incomplete remission by modified Valent criteria in 38% of patients with aggressive SM and 16% in patients with SM with associated hematological neoplasm, according to the release.

Common adverse events included nausea, vomiting, diarrhea, edema, musculoskeletal pain, abdominal pain, fatigue, upper respiratory tract infection, fever, headache, and dyspnea for these indications.

Previously, midostaurin was granted breakthrough therapy designation in AML, fast track designation in SM, and priority review, according to the FDA.