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Only 13% of US patients with CP-CML received FDA-recommended ponatinib dosing, highlighting gaps in dose optimization and the need for education.
Although the optimized and recommended regimen of ponatinib (Iclusig) is 45 mg once daily, reduced to 15 mg once daily upon achievement of BCR::ABL1 up to 1%, an analysis revealed that only 13% of patients with chronic-phase chronic myeloid leukemia (CP-CML) in the United States are being treated at that dosage, highlighting the need for more education.1
Findings presented during the
Additional findings showed that:
The mean duration of ponatinib for all patients with dose reductions was 8 months longer than those who did not, irrespective of starting dose (18.7 months vs 11.2 months).
“In this analysis, starting ponatinib at 45 mg or 30 mg [once daily] and down-dosing to 15 mg [once daily] provides 8 more months of therapy, possibly due to optimized risk:benefit,” Jorge Cortes, MD, the director of the Georgia Cancer Center at Augusta University, in Augusta, GA, and colleagues, wrote in a poster of the data. “OPTIC 5-year results suggest that ponatinib may prevent the emergence of BCR:ABL1 mutations; therefore, ponatinib should be implemented as early as indicated and dosed according to the FDA-approved dosage of 45 mg[once daily] reduced to 15 mg [once daily] upon clinical response to give pretreated patients with CML or those with the T315I mutation the greatest chance of clinical benefit.”
In December 2012, the
Data from PACE2 showed that when ponatinib was administered at a flat dose of 45 mg once daily (n = 267), it led to a 12-month major cytogenetic response rate of 56%; however, 17% of patients experienced adverse occlusive events (AOEs) that were grade 3 or 4 in severity. In OPTIC,3,4 when ponatinib was given at a once-daily dose of 45 mg until up to 1% BCR::ABL1 was achieved, and then was dose reduced to 15 mg once daily, it led to BCR:ABL1 of up to 1% rates of 52% by 12 months and 60% by 60 months. The grade 3 or 4 AOE rates at these respective time points were 6% and 7%.
“The optimal risk:benefit ratio, in a heavily pretreated population, was achieved through appropriate down-dosing from 45 mg -once daily] to 15 mg [once daily] upon clinical benefit,” the study authors wrote.1
Investigators leveraged supply chain analytics to evaluate ponatinib dosage patterns in the United States to glean insight into if patients are being dose reduced in accordance with FDA prescribing information, how they are if so, and the implications of dosage.
For the study, investigators examined ponatinib prescription information from specialty pharmacy shipment data on patients with CML between January 2021 and March 2024. “Deidentified patients receiving the FDA-recommended dosage of 45 mg [once daily] reduced to 15 mg [once daily] vs other dosing regimen variations were determined by establishing a window of first and final dosage strength,” the study authors wrote.
Patient journeys included information regarding start dosage, continuing dosage, switching dosage, discontinuation dosage, and time on therapy. They needed to have a minimum 12-month “look-forward time” after the start of treatment. Those who started and restarted with more than 3 shipments were included in the analysis to confirm that the length of the journey was adequate.
Patients were grouped into cohorts by the year and month that they began treatment. If patients had not received any subsequent shipment beyond 90 days of the last expected refill or there was a gap of longer than 90 days between current refill and next shipment or the last expected refill and end of observation, they were noted to have discontinued treatment. The last expected refill date was defined as last shipment date plus days of supply in the last shipment. They used cohort-based persistency method to determine the mean duration of treatment by starting dose and type of titration.
Investigators cited the use of specialty pharmacy shipment data as the primary data source and the use of anonymized data that does not allow further evaluation into timing or reason for dose reduction or treatment discontinuation because of safety concerns as limitations for this research.
Disclosures: Cortes noted consultancy and research funding from Sun Pharma, Novartis, Pfizer, Takeda, and BioBath Holdings. Research funding was received by Acentage. He disclosed membership on an entity’s board of directors or advisory committees for BioPath Holdings, and consultancy with Incyte, Terns, and Daiichi Sankyo.
