Thihan Padukkavidana, PhD, from Takeda Oncology, discusses post-hoc analysis data on the efficacy and safety of ponatinib in chronic-phase chronic myeloid leukemia (CML) patients. This data was presented at the American Society of Hematology Annual Meeting & Exposition (ASH 2021).
CML is a rare blood cancer characterized by the unregulated growth of myeloid cells in the bone marrow and their accumulation in the blood. Approximately 15% of new leukemia cases are CML. CML is considered very difficult to treat. Each year, there are about 8,450 new cases of CML in the United States and 1,130 will die of CML.
As Dr. Padukkavidana explains, interim analysis data from the OPTIC trial was previously presented at ASH 2020 and new post hoc analysis was recently presented at ASH 2021. The OPTIC trial is an ongoing open label phase 2 study testing different starting dosages of ponatinib (45 mg, 30 mg, 15 mg) for safety and efficacy.
The data presented at ASH 2021 showed that patients with T315I mutations had the highest ≤1% BCR-ABL1 (international scale) response rates (60%) by three years in the cohort starting at 45 mg (and dropping to 15 mg) compared with the other cohorts. Across all three cohorts analysed, 97 patients without T315I mutations (ie, no mutation or with mutations other than T315I) achieved ≤1% BCR-ABL1. Median duration of response (mDoR) for patients with a T315I mutation at baseline was 27 months for patients in the 45 mg to 15 mg cohort (n=15) and 12 months in the 30 mg to 15 mg cohort (n=5). For patients without T315I mutations, the mDoR was not reached.
Across all three cohorts, 79% of patients who achieved ≤1% BCR-ABL1 maintained this response during the study. A total of 25 patients lost responses. Of those who lost response, 11 had T315I mutations and 10 of those patient had their dose re-escalated. Among those 10 patients, six regained ≤1% BCR-ABL1 after dose re-escalation.
The most common nonhematologic treatment-emergent adverse events in the intent-to-treat population for all cohorts combined were arterial hypertension (28%), headache (18%), and lipase increased (17%). The most common hematologic treatment-emergent adverse events were thrombocytopenia (40%), neutropenia (26%), and anemia (19%). Overall, 6.0% of patients experienced a treatment-emergent arterial occlusive event; 4.6% experienced a Grade ≥3 treatment-emergent arterial occlusive event.
Next Steps
The next steps for the OPTIC trial include longer-term data to determine the long-term efficacy and safety of ponatinib in CML patients. Additionally, ponatinib is being evaluated in the PhALLCON study, a phase 3 clinical trial evaluating the efficacy of ponatinib in patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), a particularly difficult disease to treat.
For more information about CML and other rare cancers, visit checkrare.com/diseases/cancers/