Written and edited by Abel B. Daartey, PharmD

3 Key Takeaways

• In December 2023, the FDA approved DFMO, also called eflornithine or Iwilfin, to help reduce the risk that high-risk neuroblastoma comes back after intensive treatment.
• In clinical studies, children who took DFMO after standard therapy had fewer relapses than similar children who did not take it. The benefit was seen most clearly during the period when relapse is a major concern.
• DFMO is different from traditional chemotherapy. Instead of broadly attacking fast-growing cells, it blocks a growth-related pathway that many aggressive neuroblastoma tumors rely on.

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In December 2023, when I had just started my PhD journey, the U.S. Food and Drug Administration approved an old drug for a new and important purpose. The drug is eflornithine, also known as DFMO and sold as Iwilfin. It is taken by mouth after a child with high-risk neuroblastoma has already gone through intensive treatment, including anti-GD2 immunotherapy. Its goal is simple to describe, but difficult to achieve: lower the chance that the cancer comes back (6).

That matters because high-risk neuroblastoma is one of the toughest childhood cancers to treat. Many children can reach remission after surgery, chemotherapy, stem cell transplant, radiation, and immunotherapy. The problem is what happens next. Even after all of that treatment, relapse remains common, and survival after relapse is often poor (1). DFMO is aimed at this vulnerable window after remission, when doctors and families are trying to keep the disease from returning.

What the trials showed

The evidence for DFMO built over more than a decade. In a phase II study, children with high-risk neuroblastoma took DFMO by mouth twice a day for up to two years after finishing standard treatment. Two years later, 84% were alive without a relapse, progression, second cancer, or death, and 97% were alive overall (2).

Because that study did not randomly assign some children to receive DFMO and others to receive no DFMO, researchers needed to make careful comparisons. One analysis compared children who received DFMO with similar children treated at the same hospitals who did not receive it. The DFMO group did better over time. At five years, event-free survival was 85.2% in the DFMO group compared with 65.6% in the comparison group (3). In plain language, more children in the DFMO group stayed alive without the cancer returning or getting worse.

The most important comparison used patient-level data from a large Children’s Oncology Group immunotherapy trial called ANBL0032. Researchers matched children who received DFMO with similar children from that earlier trial who did not receive DFMO. In that analysis, DFMO was linked with about half the rate of relapse, progression, second cancer, or death during follow-up, and also with a lower rate of death overall (1). This evidence helped support FDA approval.

How a decades-old drug may help

DFMO is not a new molecule. It has been used for African sleeping sickness, and a related eflornithine product has been used to slow unwanted facial hair growth. What made scientists interested in DFMO for neuroblastoma was not its age, but the enzyme it blocks.

That enzyme is called ornithine decarboxylase, or ODC. ODC helps cells make polyamines. Polyamines are small molecules that cells need when they are growing and dividing. A healthy cell can often adapt when this pathway is slowed. Some cancer cells are more dependent on it.

High-risk neuroblastoma can be especially tied to this pathway because of a cancer-driving gene called MYCN. When neuroblastoma cells carry extra copies of MYCN, they tend to grow more aggressively. MYCN also helps turn on ODC1, the gene that makes the ODC enzyme (5). So the same biology that makes the tumor dangerous may also create a weakness that DFMO can target.

Laboratory studies helped build this idea. In a mouse model that develops MYCN-driven neuroblastoma, blocking ODC with DFMO reduced tumor development. The treatment also helped restore p21, a natural brake on cell division that MYCN can silence (4). This does not mean a mouse study proves the drug works in children, but it gave scientists a strong biological reason to test DFMO in patients.

The honest caveats

There are important limits to the story. The key clinical evidence did not come from a large randomized trial where children were assigned by chance to receive DFMO or not receive it. Instead, the approval relied on a single-arm study compared with carefully selected external control groups. Those methods can be useful, especially in rare childhood cancers, but they cannot remove every possible source of bias.

DFMO is also not side-effect free. The FDA label notes the need to monitor blood counts, liver tests, and hearing during treatment. Reported problems include infections, diarrhea, fever, hearing loss, and some abnormal laboratory results (7). For families, the practical message is that DFMO may be gentler than many cancer treatments, but it still needs medical supervision.

Why this one is worth watching

Much of the progress in high-risk neuroblastoma has come from adding more intense treatment. DFMO represents a different idea. It is an oral drug used after intensive therapy, at a time when the cancer may be quiet but the risk of relapse is still real. Instead of trying to kill every fast-growing cell, DFMO targets a growth pathway that aggressive neuroblastoma cells may depend on.

That is why this approval is important. It does not close the book on high-risk neuroblastoma. It does not erase the need for better randomized evidence, better relapse treatments, and long-term safety follow-up. But it gives doctors and families another tool during one of the most anxious phases of care: the period after remission, when the main question is whether the cancer will stay away.

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This article is for general education and is not medical advice. Treatment decisions for neuroblastoma should always be made with a pediatric oncology team.

References

1. Oesterheld J, et al. Eflornithine as Postimmunotherapy Maintenance in High-Risk Neuroblastoma. J Clin Oncol. 2024;42(1):90-102. https://doi.org/10.1200/JCO.22.02875
2. Saulnier Sholler GL, et al. Maintenance DFMO Increases Survival in High Risk Neuroblastoma. Sci Rep. 2018;8(1):14445. https://doi.org/10.1038/s41598-018-32659-w
3. Lewis EC, et al. A subset analysis of a phase II trial evaluating the use of DFMO as maintenance therapy for high-risk neuroblastoma. Int J Cancer. 2020;147(11):3152-3159. https://doi.org/10.1002/ijc.33044
4. Rounbehler RJ, et al. Targeting ornithine decarboxylase impairs development of MYCN-amplified neuroblastoma. Cancer Res. 2009;69(2):547-553. https://doi.org/10.1158/0008-5472.CAN-08-2968
5. Gamble LD, et al. A G316A Polymorphism in the Ornithine Decarboxylase Gene Promoter Modulates MYCN-Driven Childhood Neuroblastoma. Cancers (Basel). 2021;13(8):1807. https://doi.org/10.3390/cancers13081807
6. FDA. FDA approves eflornithine for adult and pediatric patients with high-risk neuroblastoma. December 13, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-eflornithine-adult-and-pediatric-patients-high-risk-neuroblastoma
7. DailyMed. IWILFIN (eflornithine) tablets, prescribing information. Updated March 26, 2026. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=6716d8cc-66e6-4cee-935c-ccb85ed984f5&type=display