The oral hypomethylating agent CC-486, when administered in an escalated dosing schedule (>7 days per 28-day treatment cycle), has been shown to be effective and well tolerated for patients with acute myeloid leukemia (AML) experiencing their first relapse, according to results of a study presented at American Society of Hematology (ASH) Annual Meeting.
For the phase 3 international, randomized, double-blind QUAZAR AML-001 trial (NCT01757535), 472 patients with AML were enrolled. To be eligible, participants had to be 55 years or older, with intermediate- or poor-risk cytogenetics, and have an Eastern Cooperative Oncology Group performance status score of ≤3. Patients with AML who had achieved a complete response or complete response with incomplete blood count recovery (CR/CRi) from induction chemotherapy were randomized in a 1:1 ratio to receive either 300 mg of CC-486 or placebo; both groups received treatment once daily on days 1-14 of repeated 28-day cycles. Patients who had an early AML relapse with 5-15% blasts in peripheral blood or bone marrow could escalate their dosage to 21-days/cycle.
After a median time to dose escalation of 9.2 months, results revealed that CC-486 significantly increased the percentage of patients who achieved another CR/Cri compared with the placebo arm (23% vs 11%). Median overall survival was 22.8 months in the CC-486 treatment arm compared with 14.6 months in the placebo arm. In addition, CC-486 had a significantly increased one-year survival rate compared with placebo (80.4% vs 59.5%).
The most common treatment-related adverse events reported included febrile neutropenia, thrombocytopenia, anemia, and neutropenia. Dose escalation of CC-486 did not negatively impact patient-reported quality of life scores.
Study authors, led by Hartmut Dohner, MD, a hematologist at University Hospital Ulm in Ulm Germany, conclude, "An escalated 21-day CC-486 dosing regimen was well tolerated and resulted in restoration of remission in approximately one-fourth of patients. Hematologic adverse events first reported during escalated dosing in both treatment arms may be due in part to disease relapse. A 21-day CC-486 dosing schedule could be considered for patients who experience AML relapsed with ≤15% blasts."
For More Information
Döhner H, Wei AH, Montesinos P, et al (2020). Escalated dosing schedules of CC-486 are effective and well tolerated for patients experiencing first acute myeloid leukemia (AML) relapse: results from the phase III QUAZAR AML-001 maintenance trial. ASH Annual Meeting Abstracts. Abstract 111.