Treatment for Rare Form of AML Is First New Drug in a Quarter Century

Midostaurin (Rydapt) has been approved by the FDA, in combination with chemotherapy, for the treatment of adult patients newly diagnosed with acute myeloid leukemia (AML) with a mutation in the FLT3 gene, and for adults with advanced systemic mastocytosis.

The approval followed an FDA review of phase 3 results from the RATIFY trial, conducted in 717 patients, between 18 and 60 years old, with newly diagnosed AML. The patient population was chosen following screening of about 3300 patients to identify those whose cancer harbored the FLT3 mutation, which can accelerate disease progression, increase the relapse rate, and lower survival.

Patients were treated with standard chemotherapy, with either placebo or midostaurin, which was administered at 50 mg twice daily on days 8 through 14 after chemotherapy treatment. Patients receiving midostaurin had a 23% reduction in the risk of death compared with chemotherapy alone (hazard ratio [HR] = 0.77; 95% CI, 0.63-0.95; P = .016). Further, event-free survival (EFS) was higher for the midostaurin plus chemotherapy cohort (8.2 months), compared with chemotherapy alone (3.0 months; HR = 0.78; 95% CI, 0.66-0.93; and P = .004).

EFS was defined as no complete remission within 60 days of the start of induction therapy, relapse, or death.

“The availability of midostaurin now helps to establish a new standard of care in this high-risk patient population,” 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.

Novartis, which has developed the drug, has collaborated with Invivoscribe Technologies, Inc. on the development of a companion diagnostic for midostaurin to test for FLT3-positive individuals. The LeukoStrat CDx FLT3 Mutation Assay identifies both FLT3 internal tandem duplication and tyrosine kinase domain mutations in the patient’s blood or bone marrow samples.

“Rydapt is the first targeted therapy to treat patients with AML, in combination with chemotherapy," said Richard Pazdur, MD, acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research and director of the FDA’s Oncology Center of Excellence. "The ability to detect the gene mutation with a diagnostic test means doctors can identify specific patients who may benefit from this treatment.”

Twenty percent of patients experienced the following common side effects with midostaurin: febrile neutropenia, nausea, mucositis, vomiting, headache, petechiae, musculoskeletal pain, epistaxis, device-related infection, hyperglycemia, and upper respiratory tract infection. The most common serious adverse event, observed in 16% of patients, was febrile neutropenia.