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Acute Myeloid Leukemia: New Treatment Available Thanks to Children's Mercy Research


Acute Myeloid Leukemia: New Treatment Available Thanks to Children's Mercy Research

Alan S. Gamis, MD, MPH
Associate Division Director, Section of Oncology; Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Clinical Professor of Pediatrics, University of Kansas School of Medicine
Full Biography

Children’s Mercy pediatric oncologist Alan Gamis, MD, MPH, and his team have rewritten the book on fighting acute myeloid leukemia (AML) in kids.

As lead investigator on the phase 3 Children's Oncology Group Trial AAML0531 (COG AAML0531), Dr. Gamis accomplished the extraordinary when his study spurred the FDA to announce that the drug gemtuzumab ozogamicin (MYLOTARG, Pfizer) was approved to use for pediatric patients 1 month and older.

Because most pharmaceutical research is not focused on effectiveness in children, the FDA and other regulatory agencies allow off-label use for the pediatric population. Dr. Gamis, who is also the director of the Children’s Mercy Cancer Center, said this is particularly true in pediatric oncology.

“Unbelievably, this is the first anti-cancer therapy agent that has ever been unconditionally approved for children with AML. So that’s a meaningful accomplishment,” he said. “All of the other agents we use are allowed based upon their approval in regard to other cancers or for adults with AML, but none are specifically approved for children.”

Dr. Gamis said the approval is most significant because it validates and strengthens an immunologic approach to AML therapy and elevates the standard of care for all newly diagnosed CD33-positive AML patients. It is reasonable, he said, to anticipate that standardized use of gemtuzumab ozogamicin will result in greater relapse-free survival in these patients, as this is the primary benefit seen in trials to date.

We've been able to make a number of discoveries based on our research, including the identification of a number of subtypes of AML that we didn't even know existed when we started the original trial.

Alan Gamis, MD, MPH
Director, Children's Mercy Cancer Center

A new standard of care for AML

Proving gemtuzumab’s effectiveness is only one of many revelations uncovered by the COG AAML0531 trial, Dr. Gamis said.

“That trial also had many other aspects to it, including learning more about AML itself and learning more about gemtuzumab, and not just at the clinical level but at the basic science level,” Dr. Gamis said. “We have published well over 70 publications from the trial and we're still continuing to publish 10 years out.”

“In the old days people had cancer and all cancer was assumed the same, but obviously we’ve learned that each of those individual cancers are really a compilation of many factors. So, a lot of our research has gone into identifying the genomic drivers that lead to leukemia and then lead to resistance to our normal chemotherapy agents.”

Dr. Gamis said research is under way to:

  • More accurately predict who will and will not benefit from gemtuzumab to utilize it more wisely.
  • Assess whether the degree of CD33 expression on the leukemic cell truly correlates with efficacy.
  • Determine the impact of CD33 polymorphism on efficacy.

“We've been able to make a number of discoveries based on our research, including the identification of a number of types of AML that we didn't even know existed when we started the original trial,” Dr. Gamis said. “There are subsets of people that gemtuzumab works in and subsets it doesn't so we can avoid it in those people who won't benefit.”

Dr. Gamis said this genetic mapping is allowing he and his team to further fine tune the therapy they provide to the kids at Children’s Mercy.

“It has led us to identify that for certain subtypes there are other agents that are a benefit, and that benefit is determined by the genome of the patient as well as the genome of their leukemia,” he said. “So that's now becoming a standard part of our work-up of a child with newly diagnosed cancer, in particular AML, to help us best personalize and fine tune the treatment for them.”

The wild, winding path to FDA approval 

Gemtuzumab was not always perceived as the established remedy it is today.

Approved by the FDA in 2000 for adults with AML, the organization changed course in 2010, removing it from the U.S. market when a large randomized trial determined the potential risks of the drug outweighed its potential benefits.

“When the drug was removed from the market, there were a number of other randomized ongoing adult studies that were similar to the (COG AAML0531) trial I ran at the time,” Dr. Gamis said. “Thankfully, the other adult trials showed a significant benefit, and the FDA finally re-approved it.”

Initially, the re-approval was for adults with AML and children with relapsed AML.

“Then (Pfizer) had the FDA review the data from my study,” Dr. Gamis said. “Thankfully, based on that review and of the subsequent papers we’ve published, the FDA decided to approve it all the way down to one month for children with newly diagnosed AML.”

Making connections, changing outcomes in cancer care

As a medical student, Dr. Gamis said cancer was the last thing he wanted to be involved in. Then he arrived at Children’s Mercy as a Pediatrics resident.

“I did not realize it until after I’d started, but I really enjoyed the intensity of taking care of children with cancer and knowing the tremendous amount of difference I could make for the family,” he said. “I also really enjoyed getting to know those families, taking care of them over the long course of treatment and then staying connected to them for years afterward.”

“So little was known about childhood cancer at that time that it offered an opportunity to participate, to help in really improving these lives. It all just pulled together and I became fascinated by it.”

Dr. Gamis helped oversee the opening of a new trial in 2020 to validate the earlier research. The study—COG AAML1831—is comparing standard chemotherapy to therapy with CPX-351 and/or Gilteritinib for patients with newly diagnosed AML with or without FLT3 mutations. He said the study is currently enrolling patients at over 200 institutions, one of which is Children’s Mercy, and hopes to take on roughly 1,500 patients.

“Those institutions represent about 95% of all childhood cancer centers in North America,” Dr. Gamis said. “So, when families walk through the door at one of those centers, the treating physicians will more than likely present this trial to that family to see if they would be willing to participate.”