Almost three-quarters of patients with chronic myeloid leukemia (CML) in accelerated phase (AP)/myeloid blast phase (MBP) or Philadelphia-chromosome positive (Ph+) acute myeloid leukemia (AML) responded to treatment with the combination of decitabine, venetoclax, and ponatinib, according to results of a phase II study presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.
Jayastu Senapati, MBBS, MD, of the University of Texas MD Anderson Cancer Center in Houston, Texas, and colleagues presented results of a small study of patients with CML-AP, CML-MBP, or Ph+ AML treated with decitabine 20 mg/m2 per day 5 times a day, venetoclax 400 mg equivalent dose per day for 21 days, and ponatinib 45 mg per day for 21 days in cycles 1 then continuously in cycles 2-24.
The median number of cycles received was three. In this poor-risk population of patients, 73% responded to the triplet. Forty percent of patients had complete response (CR) or CR with incomplete count recovery (CRi) and another third (33%) had morphological leukemia-free state. The majority of responders (82%) achieved their best response in cycle 1.
All patients enrolled with CML-AP responded to treatment and 82% of patients with prior tyrosine kinase inhibitor (TKI) exposure responded. Four patients were able to go on to transplant.
With a median follow-up of 9.8 months, the median overall survival was 11.0 months, with an estimated 10-month overall survival of 63%. Median relapse-free survival was 5.7 months. Among the patients that responded, five eventually relapsed, including one patient who had undergone transplant. Six patients have ongoing response.
No grade 4-5 related, nonhematological adverse events were observed. Of the 10 patients that were able to receive more than one cycle of therapy, half had a delay in initiation of subsequent cycles because of cytopenias.
Two deaths occurred during the study. One death was from leukemia, and one was from infection during morphological leukemia-free state.
Senapati J, Ravandi F, DiNardo C, et al. A phase 2 study of the combination of decitabine (DAC), venetoclax (VEN), and ponatinib in patients (Pts) with chronic myeloid leukemia (CML) in accelerated phase (AP)/myeloid blast phase (MBP) or Philadelphia-chromosome positive (Ph+) acute myeloid leukemia (AML). Abstract # e19044. Presented at the 2023 American Society of Clinical Oncology Annual Meeting; June 2-6, 2023; Chicago, Illinois.