Searching for a better way to treat Acute Myeloid Leukemia is something Alan Gamis, MD, has dedicated much of his career to at a national level.
Dr. Gamis is the Associate Division Director, Section of Oncology, and Professor of Pediatrics, University of Missouri- Kansas City School of Medicine. From 2007 to 2013, Dr. Gamis chaired the AML Disease Scientific Committee of the National Cancer Institute’s Children’s Oncology Group. As head of that program, he directed a team of world leaders in childhood AML. He has been involved in designing, overseeing and analyzing clinical trials for children the world over with this diagnosis.
|Alan Gamis, MD
"The insight we gain from being a part of these clinical trials allows us to provide children everywhere with more advanced care," Dr. Gamis said.
Dr. Gamis Presents Results of Groundbreaking Trial to National Audience
Recently, Dr. Gamis presented the results of a randomized Phase III COG trial for AML at the American Society of Hematology: "Gemtuzumab Ozogamicin (GO) in Children With De Novo Acute Myeloid Leukemia (AML) Improves Event-Free Survival (EFS) By Reducing Relapse Risk – Results From The Randomized Phase III Children’s Oncology Group (COG) Trial, AAML0531."
The trial looked at whether the addition of Gemtuzumab Ozogamicin, or Mylotarg, to standard chemotherapy improves event-free survival in pediatric AML. The study enrolled more than 1,000 children with AML over a four-year period from more than 180 institutions around the world.
Results show Mylotarg Improves Event-free Survival by Reducing Relapse Risk
The study indicates that from the time of study enrollment, gemtuzumab was significantly associated with better overall event-free survivial (hazard ratio [HzR], 0.83; P = .04) as well as relapse-free survival (HzR, 0.74 [0.6-0.93; P = .01]). Despite these improved survival rates, no significant improvement was observed for overall survival (HzR, 0.91 [0.74-1.13]).
At three years, event-free survival was 53 percent for those who had received gemtuzumab, compared with 47 percent for patients who did not.
"Event–free survival significantly improved with gemtuzumab despite no improvement of induction complete remission," said Dr. Gamis.
Relapse was significantly reduced in low risk patients. In the intermediate and high risk patients, this was limited to those who additionally received stem cell transplant in their first remission. Event-free survival and overall survival with chemotherapy intensification and transplant in AML have reached a ceiling of benefit and toxicity, commented Dr. Gamis, and gemtuzumab provides one pathway to overcome these barriers.
Applying the Lessons Learned from the Mylotarg Trial
The lessons Dr. Gamis and his colleagues have learned from the Mylotarg trial will have a ripple effect on future AML research and treatment for years to come. As part of this trial, researchers also collected genetic information specific to each child, and to the type of AML they had. Genomic research and trials being performed parallel to treatment investigations will help determine why each child responds differently to treatment depending on their metabolic and genetic make-up.
"Thanks in part to this research, we will know more about the many different kinds of AML gene mutations that drive these cancers. A real benefit will be our improved ability to better target therapy to the child’s leukemia," Dr. Gamis said.
Balancing the Risks of Drug Toxicity in Next Generation Trials
Despite reducing toxic mortality compared to the past, the experience on the gemtuzumab trial further compels researchers to search for less toxic alternatives. One finding was the risk of the toxicity of the final round of treatment outweighed the benefit.
"We did see an increase in mortality related to drug toxicity in the Mylotarg trial, especially in the patients at low risk for relapse," Dr. Gamis said. "We have taken this into account in the trials that are now enrolling patients, and we have eliminated the final round of treatment."
Currently, Dr. Gamis and his colleagues on the AML Disease Scientific Committee are designing trials that won’t open until 2020 or later.
"We are using what we have learned from the Mylotarg trial to see if we can be much more precise in our treatment to further improve survival rates for children diagnosed with AML," Dr. Gamis said. "These trials will use newer agents to target the cancer cells, yet reduce the overall exposure to chemotherapy drugs and toxicity. One day, we hope we can effectively treat children with AML without the complications we see today."