E-Newsletter - December 2015

First Targeted Therapy for Patients with High-Risk AML Significantly Improves Survival

Acute myeloid leukemia (AML) is one of the most common forms of adult leukemia. Most of the approximately 30 percent of AML patients whose leukemia cells have a mutation in the FLT3 gene have a particularly poor prognosis, as their disease tends to be more aggressive and is associated with a higher incidence of relapse. While targeted therapies have improved treatment for other blood cancers, there have been few advances in AML.

Midostaurin is an experimental drug that inhibits many enzymes, including mutant FLT3.

In a phase III, multinational, randomized trial conducted by the Alliance for Clinical Trials in Oncology (CALGB 10603), Alliance investigators led by Richard Stone, MD, of Dana-Farber Cancer Institute, analyzed whether adding midostaurin to standard chemotherapy would improve survival when compared to standard chemotherapy alone in adults aged 18 to 60 (considered “young adults”) with this mutation. Investigators randomized 717 adult patients with FLT3-mutated AML to receive either midostaurin (360) in pill form or placebo (357) in addition to standard chemotherapy followed by one year of maintenance therapy with the new drug. The median time to either failure to achieve remission, relapse, or death in patients who received midostaurin was eight months compared to only three months in the standard treatment arm. Standard chemotherapy with midostaurin and one year of maintenance therapy significantly improved median overall survival (74.7 months compared to 26.0 in the group receiving only standard therapy). Those treated with the drug had a 23 percent lower risk of death than patients receiving standard chemotherapy.

These findings, which were released in a plenary session at the 57th American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, suggest that midostaurin improves outcomes in younger adults with AML with this mutation when added to the standard chemotherapy regimen. The study also shows the value of personalizing treatment for a genetically defined subgroup of AML patients.

About 20,830 new cases of AML are expected to be diagnosed in 2015, with 10,460 deaths, according to the National Cancer Institute’s Surveillance, Epidemiology and End Results Program (SEER) reports. Children with AML can be treated with a high success rate. Most cases, however, are in adults and they are more difficult to treat, particularly the 30 percent of patients who carry the FLT-3 mutation.

“This trial is the first step in applying the theories of personalized medicine to patients with AML, specifically those patients with AML who have a FLT-3 mutation who we have shown are likely to benefit from the addition of this targeted agent, midostaurin, to standard chemotherapy,” said Dr. Stone.

Previous research suggested that individuals whose cancers lacked the FLT-3 gene mutation were not good candidates for treatment with FLT-3 inhibitors like midostaurin, but Dr. Stone said it would be worth trying the drug in those patients, as well as in older AML patients. Individuals older than 60 were not included in the trial because this chemotherapy regimen is too aggressive for them.

The study revealed no additional toxicity in the cohort that received midostaurin in addition to chemotherapy. “There was no increase in side-effects in patients assigned to midostaurin compared to those who were assigned placebo,” explained Dr. Stone. “This may have been because the side-effects of chemotherapy dwarfed any that might have been attributed to the midostaurin.”

To learn more about these findings, visit the ASH website at https://ash.confex.com/ash/2015/webprogram/Paper80269.html


For other articles in the December issue of the Alliance E-News newsletter, see below.