ASH 2024 | Five-year follow-up of OPTIC: ponatinib in CP-CML and its impact on mutational status
Jorge Cortes, MD, Georgia Cancer Center, Augusta University, Augusta, GA, comments on a five-year follow-up of the OPTIC study (NCT02467270), which investigated ponatinib in chronic-phase chronic myeloid leukemia (CML). The follow-up confirms the clinical benefit of ponatinib, particularly with the 45mg dose, with safety concerns successfully managed by reducing the dose if necessary. Notably, the study also shows that ponatinib can lead to the disappearance of mutated clones and prevent the emergence of new mutations, further supporting its use. This interview took place at the 66th ASH Annual Meeting and Exposition, held in San Diego, CA.
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Transcript (AI-generated)
The OPTIC study, just as a background, is this study where we looked at ponatinib in patients who had received two or more tyrosine kinase inhibitors or who had T315I. And the idea behind the study was to see if different doses would have, specifically lower doses, would have a better safety profile while maintaining efficacy. So patients were randomized to receive 45, 30, or 15 milligrams as a starting dose...
The OPTIC study, just as a background, is this study where we looked at ponatinib in patients who had received two or more tyrosine kinase inhibitors or who had T315I. And the idea behind the study was to see if different doses would have, specifically lower doses, would have a better safety profile while maintaining efficacy. So patients were randomized to receive 45, 30, or 15 milligrams as a starting dose. And an innovative element of this was that patients, once they responded, they were required to reduce their dose to 15 milligrams daily. The primary analysis had been reported and it showed that 15 milligrams was better. What we are showing here are two important things. One is longer follow-up, which still shows that 45 milligrams is the most effective dose. Actually the difference has increased in favor of the 45 milligrams so definitely showing that that’s the best dose to use for patients and it’s particularly true for patients with a mutation T315I. It also shows that the safety has remained very good with this approach of lowering the doses very much fewer arterial occlusive events with this approach and actually the exposure adjusted incidence is same with 45 and 30 because you quickly dose reduce. But the other element that we’re reporting for the first time here for this OPTIC study is the effect on the mutation status of patients and what we’re showing is that for many patients who had different clones with different mutations, some of these mutated clones have disappeared, have become undetectable, which is very good. And particularly that we are not seeing emergence of new clones with new mutations in patients with 45 or with 30 milligrams. Only one patient in either one of these two cohorts has had an emergent mutation, with 15 milligrams a few more. So it confirms the preclinical data that we knew that ponatinib was good in preventing emergence of mutations. So overall, it’s a study that confirms the value of ponatinib, the clinical benefit, the proper way to use it with a proper dosing and with a good safety profile.
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Disclosures
Sun Pharma: Consultancy, Research Funding; Abbvie: Research Funding; Biopath Holdings: Consultancy, Research Funding; Takeda: Consultancy; Nerviano: Consultancy; Rigel: Consultancy; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding.
