Real-world outcomes of ponatinib in heavily pretreated patients with chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia

To evaluate the real-world efficacy and safety of ponatinib, we conducted a multicenter, prospective post-marketing surveillance study in patients with chronic phase (CP), accelerated phase (AP), or blast phase (BP) chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL), who were resistant or intolerant to prior tyrosine kinase inhibitors (TKIs) or harbored the T315I mutation. A total of 148 patients were enrolled across 24 sites: 115 with CML (92 CP-CML, 12 AP-CML, 11 BP-CML) and 33 with Ph + ALL. Ponatinib was administered as third-line therapy in 70 patients (47.3%), and 127 (85.8%) initiated treatment at 45 mg once daily. Sixty-three patients (42.6%) began ponatinib due to resistance or intolerance to prior TKIs. In CP-CML, the overall major molecular response (MMR) rate was 43.2% (35/81), with a cumulative MMR incidence of 23.9% at week 24 among patients without prior MMR. In Ph + ALL, the overall MMR and complete cytogenetic response (CCyR) rates were 82.4% (14/17) and 75.0% (3/4), respectively. CP-CML patients receiving ponatinib as earlier-line therapy achieved higher MR4.5 rates than those treated later (47.4% vs. 16.1%, p = 0.011). The most common adverse drug reactions were rash (21.6%, 32/148), hypertension (12.2%, 18/148), and pyrexia (10.1%, 15/148); two vascular occlusive events occurred. Ponatinib showed favorable real-world efficacy and manageable safety in Korean patients. Early, high-dose therapy suggests a trend toward deep molecular responses, supporting its clinical benefit in real-world practice. (ClinicalTrials.gov Identifier: NCT03709017; registered October 15, 2018).