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Other TKIs
Source: Childhood Chronic Myeloid Leukemia Treatment (PDQ®)–Health Professional Version, National Cancer Institute.
Source updated: December 10, 2024 · Captured 2026-09-09.
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Context: Treatment of Childhood CML / TKI Therapy
Most data on the use of TKIs for CML is from adult clinical trials. A safe pediatric dose has not yet been established for ponatinib.
Bosutinib is a TKI that targets the BCR::ABL1 gene fusion. The FDA approved bosutinib for the treatment of all phases of CML in adults who show intolerance to or whose disease shows resistance to previous therapy with another TKI.
The pediatric recommended phase II dose of bosutinib was determined in a phase I study that included 30 screened children, 28 of whom received treatment. For children previously resistant or intolerant to other TKIs, the dose was 400 mg/m2 with food once daily (maximum dose, 600 mg). For children with newly diagnosed CML, the dose was 300 mg/m2 with food once daily (maximum dose, 500 mg).[4]
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The most prevalent adverse event (all grades) was diarrhea, which occurred in 93% of the patients, 11% of whom had grade 3 or higher severity. In some cases, the diarrhea persisted for over 1 year of treatment.
Additional adverse events of all grades (although most were grades 1–2) that occurred in over 50% of the children included nausea, vomiting, and abdominal pain.
Fifteen children discontinued use of the agent (7 were intolerant and 8 had an inadequate response).
Responses to bosutinib were considered similar to other TKIs.
Ponatinib is a BCR::ABL1 fusion transcript inhibitor that is effective against the T315I variant.[18] Ponatinib induced objective responses in approximately 70% of heavily pretreated adults with chronic-phase CML. Responses were observed regardless of the baseline BCR::ABL1 kinase domain variant.[19] The use of ponatinib has been complicated by the high rate of vascular occlusion observed in patients receiving the agent. Arterial and venous thrombosis and occlusions (including myocardial infarction and stroke) occurred in more than 20% of treated patients.[20] Ponatinib is being prospectively studied in the pediatric population.
Asciminib is an allosteric inhibitor of the myristoyl-binding pocket, whereas the previously described TKI agents target the adenosine triphosphate (ATP)–binding pocket. Asciminib was initially used to treat adults with CML that had developed resistance to the ATP-binding pocket agents.[21] Asciminib was effective in this setting, and the FDA approved it to treat CML with the T315I variant.[22] Subsequently, asciminib was approved to treat adults with newly diagnosed CML because MMR, as well as time to MMR, was significantly better with asciminib than with imatinib, and it trended similarly compared with second-generation TKIs. Safety profiles were also better with asciminib.[23] To date, there are no prospectively reported pediatric data for asciminib.
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Preserved source evidence · Not medical advice