Evaluating oral azacitidine maintenance therapy for acute myeloid leukemia

This study investigated the effectiveness of azacitidine (Onureg) tablets as maintenance therapy in patients with acute myeloid leukemia (AML) in first remission after intensive chemotherapy. The data showed that azacitidine tablets improved the survival of these patients.

Acute myelogenous leukemia (AML) is a cancer of the blood and bone marrow leading to abnormal white blood cells. AML most commonly affects adults and elderly patients. It is often treated with powerful chemotherapy. Although chemotherapy results in remission in many older patients, relapse is common and overall survival is poor. Maintenance therapy can be given to patients in remission to prevent or delay recurrence.

Azacitidine is a chemotherapy drug used for the treatment of AML. It was commonly administered by injection, but recently a tablet form was developed. It is a type of hypomethylating agent. It works by switching off a protein called DNA methyltransferase. This switches on genes that stop the cancer cells from growing and dividing. This reduces the number of abnormal blood cells and helps to control cell growth.

Patients with AML who achieve remission can benefit from a hematopoietic stem cell transplant (HSCT). This involves the transplant of blood-forming stem cells. However, many older or frail patients are not candidates for an HSCT. Therefore, chemotherapy agents such as azacitidine can be given as maintenance therapy. However, the effectiveness and safety of azacitidine tables in patients with AML in remission after first-line chemotherapy had not been investigated.

This study involved 472 patients with AML who were in complete remission after induction chemotherapy. Patients were randomly assigned to receive either azacitidine tablets (238) or a placebo (234) once daily for 14 days per 28-day cycle. The average follow-up time was 41.2 months.

The average overall survival was significantly longer in the azacitidine group compared to the placebo group (24.7 months vs 14.8 months). The average survival without relapse was also significantly longer with azacitidine than with placebo (10.2 months vs 4.8 months). It was estimated that 44.9% of patients in the azacitidine group and 27.4% in the placebo group would survive without a relapse after 1 year.

No difference was observed in the health-related quality of life between the 2 groups. Patients in both treatment arms were prone to gastrointestinal events and low platelet (blood cells involved in clotting) levels. 

The investigators concluded that azacitidine tablets used as maintenance therapy for the treatment of AML significantly improved the outcomes of patients in first remission.

This study was sponsored by Celgene, the manufacturers of azacitidine tablets. This study was the basis for the approval of azacitidine tablets as maintenance therapy for patients in first complete remission who are not candidates for intensive curative treatment.