Among patients with blast-phase chronic myeloid leukemia (CML), ponatinib with fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-IDA) may induce a second chronic phase, and may function as a bridge to allogeneic hematopoietic stem-cell transplantation (HSCT), according to research published in The Lancet Haematology.

Tyrosine kinase inhibitors (TKIs) have drastically improved outcomes among patients with CML, and have led to a near-normal life expectancy in many patients. Among patients who progress to blast phase, however—which may include up to 7% of patients who receive a TKI—outcomes remain poor. While allogeneic HSCT may be curative in this setting, a cure is contingent on remission after salvage therapy.

There is, however, no standard guidance on how best to bring patients into a second chronic CML phase. While trials relying on chemotherapy with or without TKIs have previously been conducted, the benefits remain unclear.


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Ponatinib, an oral TKI, has shown activity among patients with treatment-resistant disease. For the phase 1/2 MATCHPOINT trial, researchers aimed to determine the optimal ponatinib dose, when used with FLAG-IDA, when attempting to induce a second chronic phase among patients with CML in blast phase.

Overall, 17 patients were recruited and received ponatinib with FLAG-IDA. The median age was 33 years (range, 16-64), 71% of patients were male sex, 47% of patients had an Eastern Cooperative Oncology Group performance status of 0, 47% of patients had an additional chromosomal abnormality, and the most received prior TKI was imatinib (41%).

The median follow-up period was 41 months; the optimal ponatinib dose was determined to be 30 mg daily. Dose-limiting toxicities were noted in 4 patients, and included grade 4 increased alanine aminotransferase, grade 4 increased alanine aminotransferase, and grade 3 increased amylase.

Treatment-related mortality was, furthermore, reported in 18% (3) of patients, and was caused by cardiomyopathy, pulmonary hemorrhage, and bone marrow aplasia. After 1 treatment cycle, 69% of 16 patients were in a second chronic phase. Of the overall cohort, 71% (12 patients) received allogeneic HSCT.

“In summary, the MATCHPOINT findings suggest that ponatinib–FLAG-IDA is a feasible and active treatment strategy, tolerable to the majority of high-risk patients with myeloid, lymphoid, or mixed phenotype blast-phase chronic myeloid leukaemia,” the authors wrote in their report.

Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Copland M, Slade D, McIlroy G, et al. Ponatinib with fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor chemotherapy for patients with blast-phase chronic myeloid leukaemia (MATCHPOINT): a single-arm, multicentre, phase 1/2 trial. Lancet Haematol. Published online December 10, 2021. doi:10.1016/S2352-3026(21)00370-7