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Ponatinib and Chemotherapy for Blast Phase Chronic Myeloid Leukemia

By: Cordi Craig
Posted: Wednesday, February 12, 2020

Despite the advent of tyrosine kinase inhibitors, the survival outcomes of patients with blast phase chronic myeloid leukemia (CML) remain poor, and a standard of care has not been developed. Mhairi Copland, PhD, MBBChir, FRCP, FRCPath, of the University of Glasgow, United Kingdom, and colleagues confirmed a tolerable combination of ponatinib and conventional chemotherapy that may benefit patients with blast phase CML, even those who may have experienced disease progression on tyrosine kinase inhibitors. Results from the MATCHPOINT study were presented at the 2019 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 497) and published in the journal Blood.

“The combination of ponatinib and [conventional chemotherapy] represents a potentially important advance in the treatment of blast phase CML, a rare complication which currently has a very poor outcome,” the investigators concluded.

The research team recruited 17 patients with blast phase CML to determine the optimal dose of ponatinib in combination with conventional chemotherapy (fludarabine, cytarabine, idarubicin, and G-CSF). The research team used a statistical model that combines efficacy and toxicity to select the optimal dose.

Of the 16 patients who were evaluable for primary analysis, 4 patients experienced dose-limiting toxicities, and 3 patients died of treatment-related adverse events. However, more than half of the patients (n = 11; 69%) achieved a clinical response. Major molecular remission after the first cycle was recorded in five patients. The study team determined the optimal dose at 30 mg for ponatinib with chemotherapy. The 1-year survival rate was 45.8%. The authors suggested that the statistical model may potentially be applied to other rare malignancies.

Disclosure: For full disclosures of the study authors, visit ashpublications.org.



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