Alternative Option to Intensive Chemotherapy for Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML)

A Yale Cancer Center team has evaluated the use of hypomethylating agents in patients suffering from Acute Myeloid Leukemia (AML) who were resistant to treatment with intensive chemotherapy. Study results revealed that the complete response rate to hypomethylating agents (HMAs) in patients with refractory or relapsed AML (RR-AML) is about 16%. Among patients who achieved a complete response, the survival was significantly improved compared to those who did not respond. The findings were presented December 5, 2016 at the American Society of Hematology (ASH) meeting in San Diego.

Patients with RR-AML have poor survival and limited treatment options. HMAs are a type of epigenetic therapy that changes the methylation patterns of DNA rather than killing cells the traditional way like chemotherapy does. The two commonly used HMAs in the Unite States are azacitidine and decitabibe, although they are not yet FDA approved for this indication. In general, HMAs are better tolerated with fewer side effects compared to traditional chemotherapy. Patients are also able to receive their therapy in the outpatient setting.

Led by Maximilian Stahl, MD (first author) and Amer Zeidan, MD (senior author), study authors collected data from 11 cancer centers in the United States and Europe from 2006-2016 and analyzed the records of 656 patients treated with HMAs for RR-AML. The authors found that 16% of patients achieved complete response (CR) or complete response with incomplete count recovery (CRi). Those patients who achieved CR/CRi had a median survival of 19 months. The median survival for all patients in the study was only 6.5 months. Further analysis of the clinical and molecular predictors of response and survival is ongoing.

“These results suggest that outpatient therapy with HMAs is a reasonable option for patients with RR-AML who don’t have clinical trial options available to them,” said Maximilian Stahl, MD.

Other Yale authors include Dr. Nikolai Podoltsev, Dr. Thomas Prebet, Michelle DeVeaux, Sarah Perreault, Dr. Daniel Zelterman, Dr. Tae Kon Kim and Dr. Steven Gore.

The Use of Hypomethylating Agents (HMAs) in Patients with Relapsed and Refractory Acute Myeloid Leukemia (RR-AML): Clinical Outcomes and Their Predictors in a Large International Patient Cohort. Maximilian Stahl, MD, Nikolai A Podoltsev, MD, PhD, Michelle DeVeaux, Sarah Perreault, Pharm.D., BCPS, BCOP, Daniel Zelterman, PhD, Tae Kon Kim, MD, PhD, Thomas Prebet, MD, PhD, Steven D Gore, MD and Amer M. Zeidan, MBBS, MHS