Summary
Most patients over 75 years of age who have successfully been treated for acute myeloid leukemia may safely continue on maintenance doses of the experimental drug CC-486 without experiencing any serious side effects, according to data from the QUAZAR AML-001 clinical trial, details of which were presented at the 2020 ASCO Annual Meeting (Abstract 7530).
The experimental oral hypomethylating agent CC-486 appears to be both safe and well-tolerated as a maintenance therapy for older patients with acute myeloid leukemia (AML) in remission, as it is in younger persons, the phase III study found.
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Original Article
QUAZAR Trial Finds CC-486 Also Safe for Older AML Patients
Oncology Times
By Kurt Samson
Most patients over 75 years of age who have successfully been treated for acute myeloid leukemia may safely continue on maintenance doses of the experimental drug CC-486 without experiencing any serious side effects, according to data from the QUAZAR AML-001 clinical trial, details of which were presented at the 2020 ASCO Annual Meeting (Abstract 7530).
The experimental oral hypomethylating agent CC-486 appears to be both safe and well-tolerated as a maintenance therapy for older patients with acute myeloid leukemia (AML) in remission, as it is in younger persons, the phase III study found.
On May 1, the FDA granted priority review for CC-486 as a maintenance treatment for adult AML patients in complete remission but incomplete blood count recovery (CRi) following induction therapy with or without consolidation treatment, and who are not candidates for, or who choose not to proceed to, hematopoietic stem cell transplantation. The agency has set a goal date of September 3, 2020.
“For elderly acute myeloid leukemia patients 75 years of age or older, CC-486 appears to be able to safely provide significant gains in overall and relapse-free survival, without causing an unacceptable number of side effects or adverse events,” said Farhad Ravandi, MD, Professor and Chief of Developmental Therapeutics in the Department of Leukemia at the University of Texas MD Anderson Cancer Center.
Study Details
In the new study, a total of 460 AML patients were divided in equal halves and either treated with CC-486 or given a placebo. Their median age was 68 years. Assessment was made in three age groups, 2 weeks into treatment in a 28-day cycle, and all patients received one or more doses of CC-486.
After 2 weeks of treatment, GI issues were the most common complaints—nausea, vomiting, and diarrhea—and were slightly higher in the patients treated with CC-486. But there was little difference between the two treatment groups—those given CC-486 or not—in terms of how many patients quit the trial because they found the side effects and/or adverse events made it impossible for them to continue. No serious adverse events were reported.
“About 40-50 percent of older patients with AML attain complete remission with induction chemotherapy, but relapse is common,” Ravandi noted.
“Effective, well-tolerated maintenance therapy is needed for older AML patients in remission who are not eligible for hematopoietic stem cell transplant,” he said. “What we have found is that CC-486 seems to safely enable longer dosing schedules for therapeutic activity in this older age group.”
Ravandi, principal investigator for the QUAZAR AML-001 trial, noted that most of the side effects or adverse events have been digestive issues. In older patients over the age of 75 years, constipation was more common; however, these patients were also found to be significantly less likely to develop thrombocytopenia.
Thrombocytopenia was recorded in 37 percent of patients between 65 and 75 years of age treated with the agent, but in just 14 percent of older subjects. Neutropenia occurred in 46 percent of treated patients over 75 years of age, compared to 44 percent and 45 percent of patients in the 55-years to 65-years of age cohort, and the 65-75 years of age group, respectively.
This is a large randomized trial comparing CC-486 to placebo in patients older than 55 who had received traditional 3+7 induction, with or without consolidation, and were not eligible to undergo allogeneic stem cell transplant, had achieved complete remission or CRi and had an adequate PS of 0-2.
They were randomized 1:1 to receive either CC-486 or placebo within 4 months of achieving complete remission or CRi and continued either strategy indefinitely until relapse.
“It was a very positive study, showing a highly significant overall and relapse-free survival advantage for patients who received CC-486,” said Ravandi. “The new findings focus on patients over age 75 and show that CC-486 is just as well-tolerated in this sub-population as in younger patients, providing an overall survival and relapse-free survival advantage.”
There will be additional data gathered on residual disease through MRD monitoring by flow cytometry, which was serially performed on bone marrow sample performed every 3 months during the study.
“We feel that this will be a very important contribution for understanding MRD monitoring and therapy in AML,” noted Ravandi. “The drug is very well-tolerated, with side effects limited to GI issues. Neutropenia and thrombocytopenia can occur, but in the vast majority of cases these were grade 2 or lower.”
The data will be submitted to the FDA for approval review, Ravandi told Oncology Times.
Kurt Samson is a contributing writer.