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.
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.
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