P680: ponatinib 15 mg as consolidation prior to treatment free remission in chronic myeloid leukemia

Background: Ponatinib is a third generation TKI (3GTKI) commonly used in chronic myeloid leukemia (CML) patients with failure criteria to 2GTKI. Recently, the OPTIC trial studied the dose of 15mg compared to 30mg and 45mg showing an excellent safety profile. The role of ponatinib with the aim of treatment free remission (TFR) has not been evaluated. Our group is evaluating in two phase 2 clinical trials the use of ponatinib 15mg with the aim of consolidation prior to TFR. Aims: The aim of the study is to show interim analysis of the studies evaluating the safety of ponatinib at the dose of 15mg in CML patients with deep molecular response (DMR) for a limited period of time (1 year or 2 years) before treatment discontinuation. Methods: The PONAZERO (NCT04043676) study evaluates the use of ponatinib 15mg daily for 12 months as a consolidation strategy in CML patients that previously achieved DMR on imatinib, before treatment discontinuation. The RESTOP (NCT04160546) evaluates the use of ponatinib 15mg plus low dose aspirin for a period of time of 24 months in CML patients with DMR that previously failed to a first TFR attempt. In both studies, exclusions criteria related to cardiovascular events were followed according to OPTIC study. The incidence, nature, and severity of adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs) were graded according to the National Cancer Institute Common Terminology Criteria for AE (version 4). Results: 23 and 33 patients (n=56) were included in the PONAZERO and RESTOP trials respectively. Median ponatinib exposure was 284 days. Globally, tolerability of ponatinib 15 mg was good in most patients. Eight patients (14%) discontinued the trials due to adverse events: 1 thrombophlebitis, 2 intermittent claudication, 1 asthenia, 3 lipase increased and 1 cerebral stroke. Table 1 shows the frequency of AEs. The most common side effects (all grades) were constipation (20%), asthenia (18%), myalgia (12%), arthralgia (11%), rash (9%), bone pain (9%) and lipase increased (7%). Grade 3-4 AEs were asthenia (2%), myalgia (2%), bone pain (2%) and lipase increased (3%). 1 patient of the 56 patients analyzed (1.7%) developed an arterial occlusive event (cerebral stroke), however, two more patients developed clinical symptoms related to intermittent claudication not confirmed by analysis and/or imagines tests. Summary/Conclusion: The use of ponatinib 15mg as a consolidation strategy with the aim of TFR is safe in chronic myeloid leukemia. - Included Patients All Grade Grade 1 Grade 2 Grade 3 N = 56 N % N % N % N % Non-Hematologic AEs (2 ) Constipation 11 20% 10 18% 0 0% 1 2% Asthenia 10 18% 8 14% 1 2% 1 2% Myalgia 7 12.5% 4 7% 2 3% 1 2% Arthralgia 6 11% 5 9% 1 2% 0 0.0% Rash 5 9% 5 9% 0 0.0% 0 0.0% Bone pain 5 9% 3 5% 1 2% 1 2% Headache 5 9% 5 9% 0 0.0% 0 0.0% Essential hypertension 5 9% 4 7% 1 2% 0 0.0% Intermittent claudication 3 5% 1 2% 1 2% 1 2% Lipase increased 4 7% 1 3% 1 2% 2 3% Keywords: Chronic myeloid leukemia