Jorge Cortes, MD, Director of the Georgia Cancer Center, discusses five year follow-up results of the OPTIC clinical trial for chronic myeloid leukemia (CML).
CML is a myeloproliferative neoplasm characterized by the expression of the BCR-ABL1 fusion gene. It presents with neutrophilic leukocytosis. It can appear at any age, but it mostly affects middle aged and older individuals. Patients usually present with fatigue, weight loss, anemia, night sweats, and splenomegaly. Allogeneic stem cell transplantation and tyrosine kinase inhibitors are traditional lines of therapy for this condition.
The OPTIC clinical trial is a phase 2, randomized, open-label study evaluating the efficacy and safety of ponatinib in patients with CML. Ponatinib is a BCR-ABL1 tyrosine kinase inhibitor. Results from the five year follow-up were presented at the ASH 2024 meeting.
The primary endpoint of this study was 1% or less BCR-ABL1 at 12 months. Secondary endpoints included molecular response rates and safety outcomes. Across three randomized cohorts of 45 mg, 30 mg, and 15 mg once-daily, 283 patients were enrolled.
Results
By five years, 60% of the 45 mg cohort, 41% of the 30 mg cohort, and 40% of the 15 mg cohort achieved 1% or less BCR-ABL1. Estimated progression free survival (PFS) rates were 63% in the 45 mg cohort, 57% in the 30 mg cohort, and 60% in the 15 mg cohort. Of patients whose dose was reduced to 15 mg after achievement of 1% or less BCR-ABL1, 29% in the 45 mg cohort and 23% in the 30 mg cohort lost response following reduction. However, following reescalation, 69% in the 45 mg cohort and 80% in the 30 mg cohort regained response.
Additionally, patients with a T315I mutation at baseline had higher MR2 rates by five years, comparable to those with no mutations at baseline. As of the data cutoff, 73 patients remained on ponatinib. The most common reasons for discontinuation of treatment included adverse events, lack of efficacy, and progressive disease. The most common grade three/four adverse events were thrombocytopenia, neutropenia, and hypertension.
For more information, click here.
To learn more about CML and other rare blood cancers, visit https://checkrare.com/diseases/cancers/