Many cancer patients are benefiting from improved treatment options and survival rates. However, acute myeloid leukemia (AML) remains a particularly devastating diagnosis.
About 20,000 new cases of AML are expected to be diagnosed this year in the U.S. Statistics show that fewer than 25 percent will survive beyond five years. The blood cancer causes more than 10,000 deaths a year in the U.S. and treatment options largely have not changed in the past three decades.
That’s why The Leukemia & Lymphoma Society (LLS) dedicates a higher percentage of its research dollars toward AML than any other blood cancer. More than $21 million-- or 27 percent of the total research budget -- goes into trying to understand what causes the most common acute leukemia affecting adults and why it’s so difficult to treat.
New therapies are needed now more than ever. AML requires immediate and aggressive treatment and most patients will relapse with conventional therapies. Patients with the FLT3-ITD mutation, which is seen in about one-third of patients, have a particularly poor prognosis. Despite the millions of dollars spent on research over the past 30 years, most patients still receive the same two-drug chemotherapy cocktail.
“It’s becoming more clear that AML is a collection of distinct diseases based on the molecular profile,” said Lee Greenberger, LLS’s chief scientific officer. “Many researchers believe that targeted therapy to the molecular defect in AML patients could be very important in improving response rates.”
AML results from acquired changes in the DNA (genetic material) of a developing cell in the bone marrow. Once the cell becomes leukemic, it multiplies into 11 billion or more cells. These “leukemic blasts” build up and block the production of normal cells, ultimately taking over the rest of the body.
Researchers are studying the genetic mutations or other changes that often occur in AML in an effort to learn why these cells become abnormal. There seem to be many sub-types which affect how the leukemia will progress and which treatments might be most helpful.
“The challenge is to develop more precise therapies that cripple the cancer cells but don’t damage surrounding tissues,” said Greenberger. Molecular targets are being discovered, and a number of targeted agents are being developed to inhibit the genes responsible for the proliferation of AML cells, but they are currently only available in clinical trials.
LLS is funding a number of AML studies, including a Phase 3 clinical trial through the Therapy Acceleration Program, to advance a therapy called CPX-351, which is a different formulation of the standard therapy regimen for AML, designed to deliver a more optimal ratio of the drugs.
However, one of the most promising large-scale initiatives is Beat AML, a first-of-its-kind collaboration launched in 2013 between LLS and the Oregon Health & Science University Knight Cancer Institute to accelerate development of treatments. Beat AML is breaking new ground by creating a profile of the possible genetic drivers of AML by analyzing blood samples taken from AML patients. Researchers simultaneously test the response of patients' leukemia cells to different targeted drugs and combinations of drugs in hopes of determining which medication will be most effective in inhibiting mutations and genetic drivers of the disease. The goal is to find the right drug to give at the right time to the right patient.
The initiative acknowledges that AML is, in reality, a diverse collection of poorly understood rare diseases that share some common traits.
The project is headed up by Brian Druker, M.D., head of the Knight Cancer Institute, whose earlier research showed the efficacy of imatinib, a drug approved in 2001, which revolutionized the treatment of chronic myeloid leukemia (CML).
Through the Beat AML project, Druker and his team hope to do for patients with AML what he helped achieve with CML.
Read more about Beat AML, survivor stories and learn how to support this innovative initiative.
Dr. Brian Druker, who is leading the Beat AML initiative at the Knight Cancer Institute, looks at inhibitor trays in a team laboratory.