Efficacy and Safety of Midostaurin in Patients With Aggressive Systemic Mastocytosis or Mast Cell Leukemia

Key inclusion criteria

• Patients ≥ 18 years of age who provided written informed consent, Eastern Cooperative Oncology Group (ECOG) performance status of 0-3 and a life expectancy of >12 weeks, electrocardiogram with a QTcF of ≤ 450 ms, with a diagnosis of SM and sub-variants based on WHO criteria.
• Patients with ASM or MCL were to have one or more measurable clinical findings (termed "C-findings") and defined as those attributable to the mast cell disease component and not to AHNMD or any other cause.
• Patients with MCL were to have BM aspirate smears with ≥ 20% immature MCs. Patients with AHNMD were eligible if it was not life-threatening or in an acute stage.

Key exclusion criteria

• Patients with cardiovascular disease including congestive heart failure class III or IV according to the New York Heart Association classification, left ventricular ejection fraction (LVEF) of <50%, myocardial infarction within the previous 6 months, or poorly controlled hypertension.
• Patients with a heart block of any degree at screening (for Canada only).
• Patients with an AHNMD who required immediate cytoreductive therapy or targeted therapy (other than midostaurin).
• Patients who had demonstrated relapse after 3 or more prior regimens of SM treatment regardless of treatment regimen for supportive care (e.g., symptom-limiting therapies).
• Patients who had received any investigational agent, targeted therapy, chemotherapy, interferon-α, or 2 chlorodeoxyadenosine within 30 days prior to start of midostaurin treatment.
• Patients who had ASM with eosinophilia and known positivity for the FIP1L1- PDGFRα fusion unless they had demonstrated relapse or disease progression on prior imatinib therapy.
• Patients who had received any treatment with midostaurin prior to study entry.
• Patients who had received hematopoietic growth factor support within 14 days of Day 1 of midostaurin treatment.
• Patients who had any surgical procedure, excluding central venous catheter placement or other minor procedures (e.g. skin biopsy) within 14 days of Day 1 of midostaurin treatment.
• Patients with any pulmonary infiltrate, including those suspected to be of infectious origin. In particular, patients with resolution of clinical symptoms of pulmonary infection but with residual pulmonary infiltrates on chest x-ray were not eligible until the pulmonary infiltrates had completely resolved. Exception: patients with ASM/MCL ± AHNMD-related pleural effusion as judged by the Investigator and approved by the SSC Chairperson or designee were permitted to enter the study.