Five-year follow-up of the phase II OPTIC study

The phase II OPTIC trial evaluated three dosing strategies to optimize the efficacy and safety of ponatinib in patients with chronic phase chronic myeloid leukaemia (CP-CML) with resistance to ≥2 BCR::ABL tyrosine kinase inhibitors (TKIs), or who harbour a T215I mutation. In this video, Prof Jorge Cortes, haematologist at the Georgia Cancer Centre in Augusta, Georgia (USA), discusses the 5-year follow up data of this trial presented at ASH 2024.

OPTIC randomly assigned 283 patients to a treatment with ponatinib at a starting dose of 45, 30 or 15 mg qd. When obtaining a BCR::ABLIS level ≤1%, patients treated with the 45 or 30 mg dose lowered the ponatinib dose to 15 mg qd. Previously this trial demonstrated that patients who started the 45 mg dose had a higher likelihood of obtaining a BCR::ABLIS level ≤1% at 12 months (52% vs. 35% and 25% for the 30 and 15 mg, respectively). This benefit for the 45 mg starting dose was confirmed in this 5-year update, with 60% of patients in the 45 mg cohort obtaining a BCR::ABLIS level ≤1% as compared to 41% and 40% for the 30 and 15 mg starting dose, respectively. Similarly, also the rates of major molecular response, MR4 and MR4.5 were higher among patients who started at the 45 mg qd dose. Interestingly, the benefit observed with the 45 mg starting dose was most pronounced among patients with a T315I mutation. No difference in OS was observed between the three arms of the study.

With respect to safety the most common grade 3/4 treatment-emergent adverse events were thrombocytopenia (27%), neutropenia (18%), and hypertension (10%). Importantly, the exposure-adjusted rate of arterial occlusive events per 100 patient-years was similar across the 3 cohorts. Furthermore, mutation analyses performed in this study confirmed the ability of ponatinib to eliminate and suppress the emergence of resistance mutations when used at a starting dose of 30 or 45 mg qd.

In conclusion, these long-term data of OPTIC confirm the long-term efficacy and safety of ponatinib in patients with CP-CML. Based on these results, ponatinib should preferably be given in a response adjusted schedule with a recommended starting dose of 45 mg qd.