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Thrombocytopenia, neutropenia, and anemia have occurred in patients receiving Asciminib. Thrombocytopenia occurred in 98 of 356 (28%) patients receiving Asciminib, with Grade 3 or 4 thrombocytopenia reported in 24 (7%) and 42 (12%) of patients, respectively. Among the patients with Grade 3 or 4 thrombocytopenia, median time to first occurrence of events was 6 weeks (range, 0.1 to 64 weeks). Of the 98 patients with thrombocytopenia, 7 (2%) patients permanently discontinued Asciminib, while Asciminib was temporarily withheld in 45 (13%) patients due to the adverse reaction.
Neutropenia occurred in 69 (19%) patients receiving Asciminib, with Grade 3 and 4 neutropenia reported in 27 (8%) and 29 (8%) patients, respectively. Among the patients with Grade 3 or 4 neutropenia, median time to first occurrence of events was 6 weeks (range, 0.1 to 180 weeks) Of the 69 patients with neutropenia, 4 (1.1%) patients permanently discontinued Asciminib, while Asciminib was temporarily withheld in 34 (10%) patients due to the adverse reaction.
Anemia occurred in 45 (13%) patients receiving Asciminib, with Grade 3 anemia occurring in 19 (5%) patients. Among the patients with Grade 3 or 4 anemia, median time to first occurrence of events was 30 weeks (range, 0.4 to 207 weeks). Of the 45 patients with anemia, Asciminib was temporarily withheld in 2 (0.6%) patients due to the adverse reaction.
Perform complete blood counts every two weeks for the first 3 months of treatment and monthly thereafter or as clinically indicated. Monitor patients for signs and symptoms of myelosuppression.
Based on the severity of thrombocytopenia and/or neutropenia, reduce dose, temporarily withhold, or permanently discontinue Asciminib.
Pancreatitis occurred in 9 of 356 (2.5%) patients receiving Asciminib, with Grade 3 pancreatitis occurring in 4 (1.1%) patients. All cases of pancreatitis occurred in the Phase I study (X2101). Of the 9 patients with pancreatitis, two (0.6%) patients permanently discontinued Asciminib, while Asciminib was temporarily withheld in 4 (1.1%) patients due to the adverse reaction. Asymptomatic elevation of serum lipase and amylase occurred in 76 of 356 (21%) patients receiving Asciminib, with Grade 3 and Grade 4 pancreatic enzyme elevations occurring in 36 (10%) and 8 (2.2%) patients, respectively. Of the 76 patients with pancreatic enzymes elevated, Asciminib was permanently discontinued in 7 (2%) patients due to the adverse reaction .
Assess serum lipase and amylase levels monthly during treatment with Asciminib, or as clinically indicated. Monitor patients for signs and symptoms of pancreatic toxicity. Perform more frequent monitoring in patients with a history of pancreatitis. If lipase and amylase elevation are accompanied by abdominal symptoms, temporarily withhold Asciminib and consider appropriate diagnostic tests to exclude pancreatitis .
Based on the severity of lipase and amylase elevation, reduce dose, temporarily withhold, or permanently discontinue Asciminib.
Hypertension occurred in 66 of 356 (19%) patients receiving Asciminib, with Grade 3 or 4 hypertension reported in 31 (9%) and 1 (0.3%) patients, respectively. Among the patients with Grade 3 or 4 hypertension, median time to first occurrence was 14 weeks (range, 0.1 to 156 weeks). Of the 66 patients with hypertension, Asciminib was temporarily withheld in 3 (0.8%) patients due to the adverse reaction.
Monitor and manage hypertension using standard antihypertensive therapy during treatment with Asciminib as clinically indicated; for Grade 3 or higher hypertension, temporarily withhold, reduce dose, or permanently discontinue Asciminib depending on persistence of hypertension.
Hypersensitivity occurred in 113 of 356 (32%) patients receiving Asciminib, with Grade 3 or 4 hypersensitivity reported in 6 (1.7%) patients. Reactions included rash, edema, and bronchospasm. Monitor patients for signs and symptoms of hypersensitivity and initiate appropriate treatment as clinically indicated; for Grade 3 or higher hypersensitivity, temporarily withhold, reduce dose, or permanently discontinue depending Asciminib depending on persistence of hypersensitivity.
Cardiovascular toxicity (including ischemic cardiac and CNS conditions, arterial thrombotic and embolic conditions) and cardiac failure occurred in 46 (13%) and in 8 (2.2%) of 356 patients receiving Asciminib, respectively. Grade 3 cardiovascular toxicity was reported in 12 (3.4%) patients, while grade 3 cardiac failure was observed in 4 (1.1%) patients. Grade 4 cardiovascular toxicity occurred in 2 (0.6%) patients, with fatalities occurring in 3 (0.8%) patients. Permanent discontinuation of Asciminib occurred in 3 (0.8%) patients due to cardiovascular toxicity and in 1 (0.3%) patient due to cardiac failure, respectively. Cardiovascular toxicity occurred in patients with pre-existing cardiovascular conditions or risk factors, and/or prior exposure to multiple TKIs.
Arrhythmia, including QTc prolongation, occurred in 23 of 356 (7%) patients receiving Asciminib, with Grade 3 arrhythmia reported in 7 (2%) patients. QTc prolongation occurred in 3 of 356 (0.8%) patients receiving Asciminib, with Grade 3 QTc prolongation reported in 1 (0.3%) patient.
Monitor patients with history of cardiovascular risk factors for cardiovascular signs and symptoms. Initiate appropriate treatment as clinically indicated; for Grade 3 or higher cardiovascular toxicity, temporarily withhold, reduce dose, or permanently discontinue Asciminib depending on persistence of cardiovascular toxicity.
Based on findings from animal studies and its mechanism of action, Asciminib can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of asciminib to pregnant rats and rabbits during the period organogenesis caused adverse developmental outcomes including embryo-fetal mortality and malformations at maternal exposures (AUC) equivalent to or less than those in patients at the recommended doses. Advise pregnant women and females of reproductive potential of the potential risk to a fetus if Asciminib is used during pregnancy or if the patient becomes pregnant while taking Asciminib. Verify the pregnancy status of females of reproductive potential prior to starting treatment with Asciminib. Females of reproductive potential should use effective contraception during treatment with Asciminib and for 1 week after the last dose.
from FDA,2021.10
