SAN FRANCISCO—Dasatinib continues to demonstrate durable efficacy and benefit during a 7-year follow-up for patients with chronic-phase chronic myeloid leukemia (CML-CP) following resistance or intolerance to imatinib, especially those who achieved BCR-ABL 10% or less at 3 months, a study (Abstract 520) presented at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition has shown.
For the prospective, phase 3 study, 670 patients with imatinib-resistant or -intolerant CML-CP were randomly assigned to varying doses and frequencies of dasatinib. After 2 years, those treated with twice-daily dasatinib were allowed to switch to once daily with the same total daily dose following at least one dose reduction for certain adverse effects, and those treated with the 140 mg once daily dose could switch to the 100 mg once daily dose.
“Almost 40% of patients had been treated with imatinib for at least 3 years,” said Neil P. Shah, MD, PhD, from the University of California, San Francisco in San Francisco, CA, while presenting at the meeting. “This population was primarily resistant as opposed to intolerant,” Dr. Shah noted.
At 7 years of follow-up, progression-free survival and overall survival rates were comparable for all doses and frequencies of dasatinib studied. “Overall survival continues to be similar across the different cohorts, and the same holds true for progression-free survival,” Dr. Shah said. The proportion of patients with a best on-study major molecular response was also similar across all doses.
Patients receiving dasatinib 100 mg daily with BCR-ABL 10% or less at 3 months were found to have improved progression-free survival and overall survival rates at 7 years compared to those with BCR-ABL greater than 10% at 3 months.
For those who received dasatinib 100 mg once daily, most adverse effects first occurred within the first 2 years of treatment. The most common adverse effects were fluid retention, diarrhea, nausea/vomiting, myalgias/arthralgias, fatigue, and rash.
Patients in 100 mg daily arm had fewer cases of severe adverse effects. Pleural effusions occurred in 5% of those on dasatinib 100 mg daily and in 8% of all other arms. Over time, the risk of pleural effusion increases and “pulmonary hypertension appears to be very rare,” Dr. Shah said. In 7 years, three patients died as a result of dasatinib toxicity.
Dasatinib was well tolerated and no new safety issues were reported with dasatinib since previous analyses.
Shah, Neil P., MD, PhD, et al. “520 Seven-Year (yr) Follow-up of Patients (pts) with Imatinib-Resistant or -Intolerant Chronic-Phase Chronic Myeloid Leukemia (CML-CP) Receiving Dasatinib in Study CA180-034, Final Study Results.” ASH 2014. Oral Presentation. December 8, 2014.