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First year of ponatinib response predicts 3-year CML survival


European Hematology Association 21st Congress; Copenhagen, Denmark: 9-12 June 2016


medwireNews: An early, deep molecular response to ponatinib is a significant predictor of overall survival (OS) and progression-free survival (PFS) in heavily pretreated patients with chronic myeloid leukaemia (CML) in the chronic phase, research suggests.

The impact of landmark responses at 3, 6 and 12 months on 3-year patient outcomes for the ongoing phase II PACE trial were presented at the 2016 congress of the European Hematology Association in Copenhagen, Denmark.

The poster detailed information for 267 patients who were treated with ponatinib 45 mg/day after developing resistance and/or intolerance to imatinib and followed up for a median of 48.2 months. The majority (61%) had received three or more tyrosine kinase inhibitors previously.

At 3 months, 48% of the patients had achieved a major cytogenetic response, while 49% achieved a molecular response on the BCR–ABL International Scale of ≤10%, 34% achieved a molecular response of ≤1%, and 14% a major molecular response (MMR), defined as ≤0.1%.

By 6 months of treatment, these proportions increased to 62%, 55%, 49% and 29%, respectively, and they rose further to 71%, 60%, 54% and 39% after 12 months.

The 33 patients who achieved MMR within 3 months were younger than the 200 patients who did not (54 vs 60 years), more recently diagnosed (5.3 vs 7.6 years) and more likely to have a mutation at study entry (73 vs 44%), report Michele Baccarani, from Orsola-Malpighi University Hospital in Bologna, Italy, and co-workers.

Analysis demonstrated that PFS at 3 years was significantly predicted by BCR–ABL response at 3 months, with a 97% probability of PFS in patients with a molecular response of ≤0.1% versus 54% for those with a level >10%.

Furthermore, both 3-year PFS and OS were significantly predicted by 6-month landmark results, with the probability of PFS falling from 91% to 53% for ≤0.1% versus >10%, and that of OS falling from 93% to 78%.

Similarly, 12-month responses to treatment significantly predicted both survival outcomes at 3 years. The probability of PFS fell from 91% for those with a level of ≤0.1% to 56% for those with a BCR–ABL >10%. The corresponding values for OS were 97% and 80%.

“These data demonstrate the prognostic value of achieving early and deep landmark response with ponatinib in heavily pretreated [chronic phase]–CML patients”, the authors conclude.

But they add: “Patients who were slow to respond could still achieve the same depth of response over time; failure to respond early does not necessarily indicate a need to switch treatment – other factors should be considered when making treatment decisions.”


By Lynda Williams, Senior medwireNews Reporter

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