AML drug Komzifti added to national treatment guidelines
NCCN recommends treatment as option for some with NPM1 mutation
Komzifti (ziftomenib), a once-daily oral therapy approved for certain people with acute myeloid leukemia (AML), is now included in the National Comprehensive Cancer Network (NCCN) clinical practice guidelines in oncology for AML.
The NCCN guidelines provide evidence-based recommendations for the prevention, diagnosis, and treatment of cancer. They incorporate real-time updates to reflect rapid advancements in cancer research and care.
Komzifti, developed by Kura Oncology and Kyowa Kirin, was recently approved by the U.S. Food and Drug Administration (FDA) for adults with relapsed or refractory AML carrying a susceptible NPM1 mutation (R/R NPM1-mutated AML) who have no satisfactory alternative treatment options.
The updated guidelines list Komzifti as a Category 2A recommended treatment option for these patients, indicating a uniform consensus among the NCCN panel of experts that the therapy is appropriate based on early clinical evidence.
“The addition of KOMZIFTI to the NCCN Guidelines in Oncology underscores the potential impact of KOMZIFTI for patients with R/R NPM1-mutated AML and supports our commitment to ensuring that patients have access to this important treatment option,” Mollie Leoni, MD, chief medical officer of Kura Oncology, said in a company press release. “We are pleased to have received inclusion in the NCCN guidelines so rapidly after FDA approval and are committed to making KOMZIFTI available to patients in the United States.”
Protein-blocking treatment aims to stop disease progression
AML is an aggressive type of blood cancer. Roughly one-third of people with AML carry mutations in the NPM1 gene, which is one of the most common genetic alterations associated with the disease. These NPM1-mutated AML cases often respond to initial therapy, but they carry a substantial risk of relapse and are linked to historically poor outcomes once the cancer has relapsed or become refractory — meaning it has returned or failed to respond to prior treatment.
Komzifti is designed to block the activity of menin, a protein that helps drive uncontrolled cell growth in certain AML cells, including those with NPM1 mutations. By doing so, the therapy aims to halt cancer progression in patients with NPM1-mutated AML.
The FDA based its approval on results from the Phase1/2 KOMET-001 trial (NCT04067336). The therapy led to complete remission (cancer no longer detectable) or complete remission with partial recovery of blood counts (cancer no longer detectable, but some blood cell counts still low) in 21.4% of patients with R/R NPM1-mutated AML. Responses lasted a median of five months.
The therapy comes with a boxed warning, the FDA’s most stringent safety notice, due to the risk of differentiation syndrome (DS), a potentially life-threatening complication that can occur with certain blood cancer treatments. Symptoms of the syndrome may include fever, low blood pressure, shortness of breath, rapid weight gain or swelling, fluid around the lungs or heart, kidney problems, joint pain, and skin rashes. If DS is suspected, Komzifti treatment must be stopped immediately and managed promptly.
Komzifti also carries a risk of QTc prolongation, a type of dangerous heart rhythm disturbance also known as Torsades de Pointes that has been seen with some other blood cancer medications. Although this risk is not listed as a boxed warning, the prescribing information advises regular monitoring while patients are on therapy.
Komzifti is commercially available to U.S. prescribers and can be accessed through a limited network of pharmacies and distributors. This is a common approach for therapies that require careful monitoring and coordinated patient support due to their potential risks and complex management needs.
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