New upkeep treatment for AML shows solid advantage for patients

Overview

• Post By : Kumar Jeetendra


• Source: Weill Cornell Medicine


• Date: 23 Jan,2021

Patients with acute myeloid leukemia (AML), the most common form of leukemia in adults, that has gone into remission following initial chemotherapy remain in remission longer and have improved overall survival when they are given a pill form of the cancer drug azacitidine as a maintenance therapy, based on a randomized, international phase 3 clinical trial for which Weill Cornell Medicine and NewYork-Presbyterian are trial websites.

This is the first time that a maintenance treatment for AML has shown such a strong benefit for patients, and it’s already being adopted as part of regular care.

“At last, we have an effective treatment that may be given from the post-remission setting to keep AML patients in remission and improve their survival,” said senior author Dr. Gail Roboz, professor of medicine in the Division of Hematology and Medical Oncology and director of the Clinical and Translational Leukemia Program at Weill Cornell Medicine, a hematologist/oncologist at NewYork-Presbyterian/Weill Cornell Medical Center and principal investigator of the clinical trial at Weill Cornell Medicine and NewYork-Presbyterian. “We are especially gratified that the drug is quite well-tolerated, so that quality of life is not compromised.”

AML is a catastrophic, life-threatening hematological cancer. According to the National Cancer Institute, AML strikes roughly 20,000 people per year in the USA, and kills more than 11,000. It mainly affects middle-aged and older adults. The five-year survival rate is about 30 percent overall, but only about 10 percent for patients older than 65.

The randomized phase 3 clinical trial of 472 patients from 148 medical centers around the world, known as the QUAZAR AML-001 Trial, analyzed whether relapse could be delayed using oral azacitidine as a maintenance therapy. The investigators found that patients taking 300 mg of the medication for two weeks each month had statistically and clinically significant improvements in relapse-free survival (RFS) and overall survival (OS). Two years from the beginning of the maintenance treatment, 50.6 percent of the azacitidine patients had lived, compared with 37.1 percent of the placebo patients. Side effects were moderate and manageable.

Azacitidine is thought to work principally as a”hypomethylating” drug that eliminates chemical marks called methyl groups from DNA in cells. Methyl groups regulate gene activity, usually by silencing nearby genes, and removal of methyl groups is considered to restore action of tumor suppressor genes which offset cancerous cell proliferation.

Side effects with oral azacitidine that were somewhat more common in the treatment group included nausea, low white blood cell counts, and infections, but these were generally considered manageable and didn’t lead to treatment discontinuation. QUAZAR was the first big global AML maintenance trial to assess quality of life throughout the trial, and patients in the placebo and treatment groups scored similarly on quality of life-related steps, demonstrating the tolerability of oral azacitidine.

Dr. Roboz, who’s also a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine and a paid consultant for Celgene and Bristol Myers-Squibb, sponsors of their study, notes that some patients taking the new maintenance therapy have lived for many years.

One of my patients on the trial was so critically ill when she was initially diagnosed that she was told to get her affairs in order, but her AML was put into remission, and she has been receiving oral azacitidine maintenance therapy as part of the QUAZAR trial since 2013.”

Dr. Gail Roboz, Senior Author