Oral Form of Azacitidine Improves Overall Survival in Patients with AML in Remission

An oral formulation of azacitidine improved overall survival in patients with acute myeloid leukemia in first remission.

An oral formulation of azacitidine (CC-486) improved overall survival (OS) and relapse-free survival (RFS) in patients with acute myeloid leukemia (AML) in first remission following induction chemotherapy, according to late-breaking data presented on Tuesday at the 61st American Society of Hematology Annual Meeting and Exposition.

The results are part of the phase 3 QUAZAR AML-001 maintenance trial, which evaluated the benefit of post-remission maintenance treatment for patients with AML.

Many adult patients with AML respond to intensive induction chemotherapy, but responses are often short-lived and OS is poor. The benefit of post-remission maintenance treatment (Tx) for patients with AML is unclear, because no therapy has been shown to significantly improve OS to date.

“Currently, the only standard post-remission therapy is hematopoietic stem cell transplant, which clearly is not suitable for particularly older patients with acute myeloid leukemia,” study author Andrew Wei, MBBS, FRACP, FRCPA, PhD said in a briefing about the findings.

CC-486 is an oral hypomethylating agent that allows for prolonged drug exposure during each Tx cycle to sustain therapeutic activity.

According to Dr Wei, the authors hypothesized that giving easily delivered oral medication with extended drug exposure might have some potential for improving clinical activity.

Between May 2013 and October 2017, 472 participants with the median age of 68 years were randomized to receive CC-486 or placebo. Ninety percent of participants had de novo AML, or patients with AML with no clinical history of prior myelodysplastic syndrome, and 86% and 14% respectively, had intermediate-risk or poor-risk cytogenetics.

A 21-day dosing schedule was permitted for patients who experienced AML relapse with 5% to 15% blasts, unacceptable toxicity, or HSCT. The primary endpoint of the study was OS, whereas secondary endpoints included RFS, health-related quality of life, and safety.

The study results showed that, at median follow-up of 41.2 months, OS was significantly improved with CC-486 versus placebo. The median OS was 24.7 months versus 14.8 months from time of randomization. These findings demonstrated a statistically significant OS improvement of 9.9 months, according to Wei.

RFS was also significantly prolonged: median RFS was 10.2 months in the CC-486 arm compared with 4.8 months with placebo, according to the data. These benefits were seen regardless of the baseline cytogenetic risk, the number of prior consolidation cycles received, and CR/Cri status.

In terms of safety, adverse events were reported in ≥15% of patients in either arm. CC-486 had a manageable safety profile generally consist with injectable azacytidine. The most frequent adverse events with CC-486 were grade 1 or 2 gastrointestinal events, including nausea, vomiting, and diarrhea. The most common grade 3 or 4 adverse events were neutropenia, thrombocytopenia, and anemia.

The results are the first to validate the role of maintenance therapy in AML.

“Based on the positive results of this landmark clinical trial, we hope that maintenance therapy with CC-486 represents a new potential therapeutic standard for patients aged 55 years and older with AML in first remission,” Wei concluded.


  • Wei A, Döhner H, Pocock C, et al. The QUAZAR AML-001 Maintenance Trial: Results of a Phase III International, Randomized, Double-Blind, Placebo-Controlled Study of CC-486 (Oral Formulation of Azacitidine) in Patients with Acute Myeloid Leukemia (AML) in First Remission [LBA 3]. Presented at: The American Society of Hematology Annual Meeting and Exposition. December 10, 2019. Orlando, Florida.

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