Increasing or decreasing the dose of the second-generation TKI dasatinib based on therapeutic effect and adverse events was active and well-tolerated in older adults with chronic myeloid leukemia (CML), according to the results of a single-arm, phase-2 study.
“TKIs are commonly initiated in older patients at standard dose,” study researchers wrote. “However, because of the safety concerns of TKIs in this population, the optimal therapy for older patients has not been established.”
In this study, 52 patients aged older than 70 with newly diagnosed CML in the chronic phase were given oral dasatinib at a starting dose of 20% of the standard dose (20 mg/day). Treatment was assessed at 3 months, 6 months, and 9 months, and if adverse events were grade 2 or better, the same dose was continued. When response was suboptimal and adverse events were grade 2 or better, the dose was increased by 20 mg per day. If a dose reduction was made because of grade 3 or worse adverse events, no further increases were made.
The median age at diagnosis for included patients was 77.5 years. Sixty percent of patients reached major molecular response at 12 months, with a median follow-up of 366 days.
“The calculated major molecular response was higher than the lower confidence limit of 38%, which was set according to results from the DASISION trial and took into account a non-inferiority margin of 10% (P=0.0007),” the researchers wrote.
Grade 3/4 adverse events were reported in 23% of patients. Neutropenia was the more frequent grade 3/4 adverse event. Five patients had median dose interruptions of 7 days due to hematological and non-hematological events. Three patients required dose reduction to 20 mg every other day. One patient discontinued therapy for drug-related toxicity.
“Our findings together with previous studies on reducing the dose of dasatinib suggest that the standard dose (100 mg/day) is not absolute and dasatinib should be used with an appropriate reduced dose in older patients with chronic myeloid leukemia in the chronic phase,” the researchers concluded.
