Ponatinib as second-line treatment in chronic phase chronic myeloid leukemia patients in real-life practice

Abstract

Scarce information is available on the use of ponatinib as second-line treatment in chronic phase chronic myeloid leukemia (CP-CML) patients resistant and/or intolerant to prior tyrosine kinase inhibitor (TKI) therapy. We collected data from 29 CML patients, with a median age of 54 years (range 32-72). Eleven patients had received dasatinib, 15 patients received nilotinib, and 3 patients received imatinib as first-line treatment. Forty-five percent of patients started ponatinib for secondary resistance, 38% for primary resistance, 7% for severe intolerance associated to a molecular warning, 7% due to the presence of a T315I mutation, and 3% for severe intolerance. Ponatinib was started at a dose of 45 mg in 60% of patients, 30 mg in 38%, and 15 mg in 2% of patients. Overall, at a median follow-up of 12 months, 85% of treated patients improved the level of response as compared to baseline, with 10 patients achieving a deep molecular response (MR4-4.5). No thrombotic events were recorded. The dose was reduced during treatment in 2 patients due to intolerance and in 8 patients in order to reduce the cardiovascular risk. Ponatinib seems a valid second-line treatment option for chronic phase CML, in particular for patients who failed a front-line second-generation TKI due to BCR-ABL-independent mechanisms of resistance.

Ponatinib in the Treatment of Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Leukemia: Recommendations of a German Expert Consensus Panel with Focus on Cardiovascular Management

“…Moreover, patients with primary cytogenetic resistance to first-line (or second-line) therapy seem not to benefit as much from sequential therapy with 2G TKIs as from ponatinib [22]. Retrospective real-world studies showed favorable outcome with second-line ponatinib in CP-CML after previously failing one 2G TKI: an Italian case series reported outcomes in 29 patients with R/I to first-line TKI treatment who switched to ponatinib 45 mg, or to 30 mg or 15 mg in the presence of CV risk factors [23]. After a median of 12 months, response versus baseline was improved in 85.7% of patients.…”

“…The OPTIC trial comparing 15, 30, and 45 mg in patients with R/I CP-CML is currently evaluating whether a lower ponatinib starting dose would be noninferior and safer (ClinicalTrials.gov Identifier: NCT02467270). To date, there are only retrospective data available from an Italian case series which evaluated ponatinib in second-line [23]. Eleven of 29 patients were started on lower-dose ponatinib because of older age or other risk factors such as hypertension, diabetes, or hypercholester­olemia.…”

Arterial occlusive events in chronic myeloid leukemia patients treated with ponatinib in the real‐life practice are predicted by the Systematic Coronary Risk Evaluation (SCORE) chart

“…2 The incidence rate of AOEs following ponatinib treatment in real life was reported only in a few small patient cohorts followed up for short periods, showing variable outcomes. [3][4][5][6] Risk factors associated with the development of AOEs have been identified in basal CV risk factors and/or may include the following: a history of previous ischemic disease, 2 dose intensity and age at starting ponatinib, 7 male sex, previous history of AOEs, and previous exposure to nilotinib. 5 The usefulness of the Systematic Coronary Risk Evaluation (SCORE) risk assessment at disease baseline, a 10-year risk estimation of fatal CV disease based on sex, age, smoking, systolic pressure, and total cholesterol level, to identify patients with increased risk of occurrence of AOEs during ponatinib treatment has been suggested.…”

The multi‐tyrosine kinase inhibitor ponatinib for chronic myeloid leukemia: Real‐world data

“…Ponatinib improved the level of response from baseline levels in 86% of patients (Table 2). The most common AEs were thrombocytopenia grade 3, skin rash, hypertension, neutropenia grade 3, and increased lipase; no other cardiovascular AEs were observed (Table 2).…”