nbsp;71 20 69 16
Hypernatremia 21 1 15 2
Hypocalcemia 74 7 70 8
In Study 1, 205 patients (120 in RYDAPT arm and 85 in placebo arm) who remained in remission following completion of consolidation continued to receive either single agent RYDAPT or placebo for a median of 11 months (range 0.5 to 17 months) with 69 in the RYDAPT arm and 51 in the placebo completing 12 treatment cycles. Common adverse reactions (greater than or equal to 5% difference between the RYDAPT and placebo arms) reported for these patients included nausea (47% vs. 18%), hyperglycemia (20% vs. 13%) and vomiting (19% vs. 5%).
Systemic Mastocytosis
Two single-arm, open-label multicenter trials (Study 2 and Study 3) eva luated the safety of RYDAPT (100 mg twice daily with food) as a single agent in 142 adult patients total with ASM, SM-AHN, or MCL. The median age was 63 (range: 24 to 82), 63% had an ECOG performance status of 0 or 1, and 75% had no hepatic impairment (bilirubin and AST ≤ ULN) at baseline. The median duration of exposure to RYDAPT was 11.4 months (range: 0 to 81 months), with 34% treated for ≥ 24 months.
The most frequent adverse reactions (≥ 20%), excluding laboratory terms, were nausea, vomiting, diarrhea, edema, musculoskeletal pain, abdominal pain, fatigue, upper respiratory tract infection, constipation, pyrexia, headache, and dyspnea (Table 4). Grade ≥ 3 adverse reactions reported in ≥ 5%, excluding laboratory terms, were fatigue, sepsis, gastrointestinal hemorrhage, pneumonia, diarrhea, febrile neutropenia, edema, dyspnea, nausea, vomiting, abdominal pain, and renal insufficiency (Table 4).
Adverse reactions led to dose modifications (interruption or reduction) in 56% of patients. Among these, the most frequent adverse reactions (> 5%) were gastrointestinal symptoms, QT prolongation, neutropenia, pyrexia, thrombocytopenia, gastrointestinal hemorrhage, lipase increase, and fatigue. The median time to first dose modification for toxicity was 1.6 months, with 75% of dose modifications first occurring within 5 months of starting treatment.
Treatment discontinuation due to adverse reactions occurred in 21% of patients. The most frequent adverse reactions causing treatment discontinuation included infection, nausea or vomiting, QT prolongation, and gastrointestinal hemorrhage.
Serious adverse reactions were reported in 68% of patients, most commonly (≥ 20%) due to infections and gastrointestinal disorders.
On-treatment deaths unrelated to the underlying malignancy occurred in 16 patients (11%), most commonly from infection (sepsis or pneumonia), followed by cardiac events. Of the on-treatment deaths from disease progression, 4 were also attributable to infection.
Table 4 summarizes the adverse reactions reported in ≥ 10% of the patients with advanced SM.
Table 4: Adverse Reactions Reported in ≥ 10% of Patients with Advanced SM (Study 2 and Study 3)
RYDAPT (100 mg twice daily)
N=142
Adverse Reaction a All Grades
% Grade ≥ 3
%
Gastrointestinal disorders
Nausea 82 6
Vomiting 68 6
Diarrhea a 54 8
Abdominal pain a 34 6
Constipation 29 < 1
