Lower-dose ponatinib has demonstrated efficacy as induction in patients with chronic phase chronic myeloid leukemia (CML), according to research presented at the ASH Annual Meeting 2023.
“[P]onatinib exerts an excellent antileukemic activity as front-line therapy of chronic phase CML at 30 mg daily,” said study presenter Franck E. Nicolini, MD, PhD, of the Centre Léon Bérard in Lyon, France.
Dr Nicolini reported that rates of cardiac and vascular toxicity were low, but these events should be detected as soon as possible.
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Dr Nicolini and colleagues tested upfront ponatinib in chronic phase CML in the phase 2 TIPI trial (ClinicalTrials.gov Identifier: NCT04070443). The trial is designed to test 6 months of ponatinib induction followed by consolidation with imatinib, but Dr Nicolini presented results after ponatinib treatment alone.
Enrolled patients are intended to receive ponatinib at 30 mg per day for 6 months. Induction is followed by consolidation with imatinib at 400 mg per day until treatment-free remission, defined as a molecular response with a 4.5-log reduction (MR4.5) that is sustained for at least 2 years.
The trial enrolled and treated 169 patients with chronic phase CML. Their median age at baseline was 48 (range, 18-65) years, and 67% were men.
Patients received ponatinib for a median of 174 days, and the median follow-up was 18 months.
At 1 month, 93% of patients had a complete hematologic response, and 97% had an early molecular response. At 3 months, 70.5% had a complete cytogenetic response.
At 6 months, 57% of patients had achieved a major molecular response, 30% had achieved an MR4, 11% had an MR4.5, and 8.3% had an MR5.
The event-free survival rate at 6 months was 90.53%. The events included 2 deaths — 1 sudden cardiac death and 1 transplant-related death — as well as 14 adverse events (AEs) that led to permanent treatment discontinuation.
Overall, there were 135 grade 3-5 AEs, and 109 were related to study treatment. Hematologic AEs occurred in 29.5% of patients. The most common were thrombocytopenia (14.5%) and neutropenia (10.5%).
Nonhematologic AEs occurred in 51.0% of patients. The most common were increased liver enzymes (12%), vascular events (10.0%), and lipase elevation (9.0%). Of the 17 vascular AEs, 15 were hypertension, 1 was a pulmonary embolism, and 1 was carotid stenosis.
Six patients (4.5%) experienced grade 3-5 cardiac events, including the sudden death. An independent data monitoring committee determined that this death was probably not related to study treatment, Dr Nicolini said.
He stressed, however, that cardiovascular toxicity “needs to be prevented and cautiously detected as soon as possible.”
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Nicolini FE, Charbonnier A, Escoffre-Barbe M, et al. Trial of imatinib after ponatinib induction (TIPI) in the front-line treatment of chronic phase (CP) chronic myeloid leukemia (CML) setting. Report of the first therapeutic sequence. Presented at ASH 2023. December 9-12, 2023. San Diego, CA. Abstract 445.
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