ATLANTA – A paradigm shift is underway in the treatment of acute myeloid leukemia: The newest of personalized medicines proved more effective and less toxic than standard chemotherapy for certain acute myeloid leukemia patients, new research indicates.

Acute myeloid leukemia, often called AML, is a type of blood and bone marrow cancer. Patients with a mutation of the FLT3 gene — about 30% of all AML patients — have a higher risk of relapse.

The new research involved patients with relapsed or refractory AML who tested positive for the FLT3 mutation.

In a clinical trial, rates of complete remission were 34% for those receiving the new drug, gilteritinib, compared with just 15.3% for those given standard chemotherapy, explained Dr. Alexander Perl, lead study author and an associate professor at the Perelman School of Medicine at the University of Pennsylvania.

Perl presented the results at the annual meeting of the American Association for Cancer Research in Atlanta on Monday. The research was funded by Astellas Pharma US, maker of gilteritinib (brand name Xospata).

Mutation drives the growth of leukemia cells

In the United States last year, 19,520 people were diagnosed with AML, and more than half — about 10,670 — died of the disease, according to the National Cancer Institute. The most recent statistics suggest that 27.4% of patients will live five years after their diagnosis.

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“Relapsed” disease means a patient achieved remission but the cancer returned, and “refractory” disease means chemotherapy didn’t work and “the disease grew straight through it,” Perl said. When it comes to AML, “if you ever relapse or if don’t respond to front-line chemotherapy, survival is very poor.”

The FLT3 mutation drives the growth of leukemia cells. It’s similar to a car that races forward without you stepping on the gas pedal, Perl said; gilteritinib, which was approved by the US Food and Drug Administration in November, essentially stops the fuel from getting to the engine by directly targeting the gene.

For the new study, 247 patients with relapsed or refractory AML and the FLT3 mutation were randomly assigned to receive gilteritinib, and 124 similar patients were assigned to standard chemotherapy.

Gilteritinib is a pill that’s taken daily until a response is seen, though that can take more than a month, Perl said. By comparison, some types of chemo to treat AML are so toxic that patients must be hospitalized to both receive and recover from the treatment.

Study patients receiving gilteritinib had a 36% reduction in risk of death compared with the chemo patients, the results showed. Twelve months after treatment began, 37.1% of the gilteritinib patients were alive, compared with 16.7% of chemo patients, although overall average survival was just 9.3 months and 5.6 months, respectively.

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The longest survival among gilteritinib patients was seen in those who had a stem cell transplant and then resumed taking gilteritinib to prevent a relapse, but long-term survival was very uncommon among either group of patients, Perl said. Only 26 gilteritinib patients and 15 chemo patients had the transplant. Still, the clinical trial showed an overall positive result.

And rates of complete remission with either full recovery of blood counts or partial recovery of blood counts was 34% for gilteritinib patients, compared with 15.3% for chemo patients, Perl said.

Side effects of gilteritinib include drops in blood counts, which are also seen in chemo patients, as well as infections and fevers, which are common in leukemia patients.

“We’ve proven that one therapy is better than another,” Perl said, adding that this immediately changes how doctors treat patients and improves the standard of care.

AML: A ‘warlike situation’

Dr. Mrinal Patnaik, a hematologist at Mayo Clinic said the study results and FDA’s approval of gilteritinib are “very encouraging.”

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“I trained in the early 2000s, when there was not a single oral agent for the management of AML,” said Patnaik, who was not involved in the new study. “One of my professors had told me that AML was akin to a warlike situation where sometimes, you had to bomb the village in order to save it. We would throw these drugs that would kill everything and hope patients would recover with normal bone marrow.”

In the past two years, at least four new personalized medicines targeting key genes have “given patients much better outcomes and have changed the landscape of how we manage acute leukemia,” he said. It’s a “paradigm shift.”

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Dr. Gwen Nichols, chief medical officer of The Leukemia & Lymphoma Society, wrote in an email that “we don’t have enough information yet to speak to how patients are responding to this drug outside of the clinical trials, but the results of this study are certainly encouraging.”

Nichols, who also was not involved in the study, said the FDA is looking at other drugs for AML, but the “bottom line” is that FLT3-positive AML is a “bad prognosis,” so it is “good to have several options now showing better efficacy as compared to standard care.”

Nichols noted that The Leukemia & Lymphoma Society’s is conducting a clinical trial testing gilteritinib as a frontline therapy for AML patients.

“Ultimately, the best outcomes for FLT3 positive and other AML patients will likely be from combination therapies,” she said.