Newly Approved Agent Fills Gap in Therapy for High-Risk AML


The US Food and Drug Administration recently approved a new agent for treatment of adult patients with relapsed or refractory acute myeloid leukemia.

The US Food and Drug Administration (FDA) recently approved gilteritinib (Xospata) for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation as detected by an FDA-approved test. In conjunction, the FDA also approved an expanded indication for a companion diagnostic to detect this mutation, the LeukoStrat CDx FLT3 Mutation Assay, to include use with gilteritinib.

Until now, clinicians have had no specific therapies beyond chemotherapy available to treat high-risk patients with AML.

Approval of gilteritinib was based on an interim analysis of the ADMIRAL trial (NCT02421939), which included 138 adult patients with relapsed or refractory AML with a FLT3 ITD, D835, or I836 mutation. Gilteritinib was given orally at a dose of 120 mg daily until unacceptable toxicity occurred or no clinical benefit was seen. After a median follow-up of 4.6 months (range, 2.8–15.8), 29 patients (21%) achieved complete remission (CR) or CR with partial hematologic recovery (CRh).

The most common adverse reactions occurring in ≥ 20% of patients were myalgia/arthralgia, elevated transaminase level, fatigue/malaise, fever, noninfectious diarrhea, dyspnea, edema, rash, pneumonia, nausea, stomatitis, cough, headache, hypotension, dizziness, and vomiting.

Led by Alexander Perl, MD, an associate professor of Hematology/Oncology in the Perelman School of Medicine at the University of Pennsylvania and the Abramson Cancer Center in Philadelphia, the ADMIRAL Trial is still ongoing. However, an interim analysis showed significantly more CR or CRh among gilteritinib-treated patients compared with those randomized to receive standard chemotherapy.

Perl explained that salvage therapy is used to stabilize aggressive leukemia before a patient receives a bone marrow transplant. Administration of a low-toxicity but highly-active drug, like gilteritinib, makes it more likely that relapsed or refractory patients undergo transplant, remain stronger at the time of transplant, and are better able to withstand the surgery and recovery, according to Perl.

“For an oral agent with a relatively safe toxicity profile to achieve such excellent outcomes is great news for AML patients,” Pankit Vachhani, MD, an assistant professor of medicine in the Division of Hematology/Oncology at UAB Comprehensive Cancer Center in Birmingham, Alabama, said in an interview with Cancer Network. Besides the notable CR/CRh rates, about one-third of transfusion-dependent patients became transfusion-independent, while about 50% of transfusion-independent patients maintained transfusion independency during the 56-day post-baseline period, Vachhani said.

Gilteritinib is one of three newly approved oral agents for AML. The others are venetoclax and glasdegib, which were both approved for use in essentially the same population, newly diagnosed and older patients who, by age or comorbidities, have not benefited from more intensive approaches.

“Although durable responses can be seen with either agent’s regimens, neither of these drugs is expected to be curative in this setting, and I predict both will get used widely, most likely in sequence,” Perl told Cancer Network.

Vachhani said he expected that a fourth agent, also a FLT3 inhibitor, will be approved within the next few months. “We are truly in a new era of personalized medicine with less toxic and targeted therapies for AML,” said Vachhani.

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