Highlights from

ASH 2020

62nd Annual Meeting & Exposition of the American Society of Hematology

Virtual 5 - 8 December 2020

Ponatinib provides a therapeutic option for leukaemia patients who have failed previous TKI therapy

Researchers presented results of their interim analysis on the largest population of patients to date receiving second-generation tyrosine kinase inhibitors (TKIs). Ponatinib elicited high response rates and favourable survival rates, accompanied by a manageable safety profile [1].

In patients with chronic phase-chronic myeloid leukaemia (CML) who have failed to respond to both first-line and second-generation TKIs, there is a lack of evidence to justify further attempts at management with an alternate second generation TKI.

The PACE trial (NCT01207440), completed in January 2019, demonstrated a dramatic and durable antileukemic response elicited by a 45 mg daily dose of ponatinib (a multi-targeted TKI), in patients with either CML or Philadelphia chromosome-positive acute lymphoblastic leukaemia. Adverse events included thrombocytopenia (37% of patients) and serious arterial thrombotic events (9% of patients) [2]. Post hoc modelling of PACE data suggested a relationship between adverse events and dosage; researchers designed a trial to explore this relationship.

The OPTIC trial (NCT02467270), initiated in June 2015, is a study in progress that has randomised 276 participants to receive 1 of 3 different dosages of ponatinib (15, 30, or 45 mg daily), and will characterise efficacy and safety of ponatinib over these 3 doses. Furthermore, OPTIC implements a response-adjusted dosing regimen: the dosage of the cohort that begins at a dosage of 45 mg daily will have their dosage of ponatinib reduced to 15 mg daily upon achieving the treatment response threshold. Efficacy data will consist of molecular responses and survival outcomes; safety data will include treatment-emergent rates of arterial occlusive events. The OPTIC study will also analyse treatment response according to mutation status.

Interim analysis of data combined from 350 patients from both OPTIC and PACE trials reveals efficacy outcomes comparable to those seen in the PACE trial alone. Incidences of adverse events, including arterial occlusive events were lower.

  1. Kantarjian H, et al. Efficacy and Safety of Ponatinib (PON) in Patients with Chronic-Phase Chronic Myeloid Leukemia (CP-CML) Who Failed One or More Second-Generation (2G) Tyrosine Kinase Inhibitors (TKIs): Analyses Based on PACE and Optic. 62nd ASH Annual Meeting, December 5-8, 2020. Abstract 647.

  2. Cortes JE, et al. N Engl J Med 2013 Nov 7;369(19):1783-96.

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