Benefit-Risk Assessment
arterial occlusive, toxicity, CML-CP, cardiovascular toxicity, Myelosuppression
ADVERSE EVENTS, CML, ADVERSE EVENT, EVENTS, MYELOSUPPRESSION
As mentioned previously, superiority of asciminib over bosutinib in patients previously treated with 2 or more TKIs was demonstrated in the pivotal ASCEMBL study. The efficacy of asciminib as compared to bosutinib was demonstrated in patients who received 2, 3, or at least 4 prior TKI therapies (24 weeks MMR rate of asciminib vs. bosutinib: 2 prior TKIs 30.3% vs. 18.2%, 3 prior TKIs 22.6% vs. 12.1%, and 4 or more prior TKIs 6.7% vs. 0%). Using MMR rate as a surrogate endpoint for overall survival is well established in CML clinical trials and treatment guidelines.Bosutinib was agreed to be a valid comparative therapy, as it has been approved by the European Commission for the indication of CML-CP previously treated with at least 2 TKIs.The asciminib cohort of the ASCEMBL study showed less adverse events than the bosutinib cohort resulting in a favorable relative safety profile. Myelosuppression was reported as a severe adverse event in the asciminib cohort, but it was reversible and managed by temporarily withholding treatment. Clinical safety results were supported by data from one arm of the independent, phase I open-label X2101 study which treated CML-CP patients with single-agent asciminib at different doses. Regarding clinical safety, the assessment of cardiovascular toxicity such as arterial occlusive events was highlighted, as it is a known toxicity of ponatinib treatment.