Dr Kantarjian on the Predictive Value of Early Responses to Ponatinib in CP-CML

Hagop M. Kantarjian, MD, professor and chair of the Department of Leukemia and the Samsung Distinguished Leukemia Chair in Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses the predictive value of early landmark cytogenetic or molecular responses to ponatinib (Iclusig) in heavily pretreated patients with chronic-phase chronic myeloid leukemia (CP-CML).

The sequential use of BCR::ABL1 TKIs or the presence of BCR::ABL1 mutations are associated with poor outcomes in patients with CP-CML. In December 2020, the FDA approved the BCR::ABL1 TKI ponatinib for the treatment of patients with CP-CML that is resistant or intolerant to at least 2 prior kinase inhibitors. That regulatory decision was supported by data from the phase 2 OPTIC (NCT02467270) and PACE (NCT01207440) trials. Although historical data have shown that early landmark responses to BCR:ABL1 TKIs in newly diagnosed patients with CP-CML are associated with improved long-term outcomes, less data are available for heavily pretreated patients, Kantarjian says.

Kantarjian and colleagues presented findings from a post-hoc analysis of the PACE study at the 2023 SOHO Annual Meeting. The analysis examined the long-term outcomes of patients treated with ponatinib who experienced landmark cytogenetic and molecular responses at 3, 6, or 12 months. Data showed that major molecular responses (MMRs) achieved with ponatinib at 3 months were associated with improved 4-year progression-free survival (PFS) and overall survival (OS) rates vs those without MMR at that time point. This correlation was not observed at the 6- and 12-month time points, Kantarjian adds.

The findings for patients who achieved an early molecular response could help inform the selection of heavily pretreated patients who could benefit from treatment with ponatinib, Kantarjian concludes.