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Combined tebentafusp and SBRT showed disease control in a patient with metastatic uveal melanomaOne Woman’s Rare Eye Cancer Spread. Then a New Combo Stopped It Cold

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Key Takeaway
Consider tebentafusp combined with SBRT for metastatic uveal melanoma, noting potential synergy in this single case.

This case report details the experience of a single 39-year-old woman with localized uveal melanoma who subsequently developed metastases in the liver and hilar adenopathies. The patient was treated with a combination of tebentafusp and stereotactic body radiotherapy (SBRT). The setting and specific funding sources were not reported.

Imaging assessments revealed that after four months of tebentafusp therapy, the patient exhibited oligoprogression in a hilar adenopathy, while hepatic lesions remained stable. By the nine-month mark, MRI demonstrated a partial response across all lesions. Following the initial four months of therapy, disease control was maintained for an additional 35 months.

Regarding secondary outcomes, the patient reported excellent quality of life throughout the observation period. Her ECOG Performance Status remained at 0. No adverse events, serious adverse events, or discontinuations were reported, and the treatment was described as well tolerated.

The authors note that this case suggests a synergistic interaction between ImmTAC-mediated T-cell activation and radiation-induced immunogenic modulation. However, because this is a case report, the certainty is limited. Prospective studies are warranted to evaluate this combination and identify biomarkers predictive of response.

A Rare Cancer Returns

Seven years after beating eye cancer, Sarah faced a new fear. The cancer was back. It had spread to her liver and lymph nodes. For many, this news would mean time is running out.

Sarah was only 39. She had a rare eye cancer called uveal melanoma. It’s not the same as skin melanoma. It starts inside the eye. It’s stubborn. And once it spreads, treatment options are very limited.

But Sarah’s story took a different turn. A turn that gives hope to others in her shoes.

Uveal melanoma is rare. Only about 2,000 to 3,000 people in the United States are diagnosed each year. But it’s aggressive. About half of all patients will see their cancer spread, often to the liver.

Until recently, there was little doctors could do once it spread. Chemotherapy doesn’t work well. Newer immune drugs help some, but not everyone. And for many, the cancer eventually finds a way around them.

That’s why this case stands out. It shows what might be possible when two powerful treatments are used together in a smart way.

The Old Way vs. A New Idea

In the past, doctors often used radiation to shrink a tumor and stop it from growing locally. They didn’t think of it as a way to boost the immune system.

But research has changed that thinking.

Radiation can do more than kill cancer cells. It can also act like a flare signal. When cancer cells die from radiation, they release tiny pieces of the tumor. These pieces act like flags. They tell the immune system, “Here’s the enemy. Come get it.”

This is called immunogenic cell death.

Tebentafusp is a new type of drug. It’s not traditional chemotherapy. It’s a “guided missile” for immune cells. It links a cancer-finding part to an immune-cell activator. It tells T-cells (your body’s soldiers) to attack cancer cells that carry a specific marker, called gp100.

But even this smart drug can use a boost. That’s where radiation comes in.

Think of a tumor as a locked fortress. The immune system can’t always get in.

Tebentafusp is like a key that unlocks the door. It finds the gp100 marker and guides T-cells straight to the cancer.

Radiation is like a battering ram. It smashes the walls. When it does, it releases more cancer markers into the body. This gives the T-cells more targets to see and attack.

Together, they don’t just attack the fortress. They teach the immune system to recognize the enemy better. This can lead to what doctors call an “abscopal effect.” That’s when treating one tumor helps shrink tumors elsewhere in the body.

A Closer Look at the Case

The study, published in Frontiers in Medicine, describes a real patient. A 39-year-old woman. She had uveal melanoma that came back seven years after her first treatment.

Her cancer had spread to her liver and lymph nodes. She tested positive for HLA-A*02:01, a genetic marker needed for tebentafusp to work.

She started tebentafusp. It was well tolerated. After four months, most of her cancer was stable. But one lymph node near her lungs was growing.

Doctors didn’t stop treatment. Instead, they added targeted radiation to that one spot. This is called stereotactic body radiotherapy (SBRT). It delivers a high dose of radiation very precisely.

She continued tebentafusp during and after radiation.

The results were striking.

Nine months after starting the combo, scans showed the cancer had shrunk in all her lesions. Not just the one that got radiation. The liver tumors were smaller too.

She stayed on tebentafusp. For the next 35 months, her cancer remained under control. She had no major side effects. She lived a normal, active life.

That’s a total of three years of disease control after metastasis. For uveal melanoma, that’s a meaningful stretch.

But Here’s the Catch

This is one patient. One story. Not a clinical trial with hundreds of people.

We don’t know if this will work for everyone. Some patients may not respond. Others might have side effects. And tebentafusp only works for people with the HLA-A*02:01 marker, which is about half of those with uveal melanoma.

Where This Fits In

Doctors are excited about this case because it shows a clear path forward. Radiation isn’t just a local fix anymore. It can be part of a systemic strategy.

This doesn’t mean this treatment is available yet.

Right now, tebentafusp is approved for metastatic uveal melanoma in some countries. Radiation is widely available. But using them together like this is still experimental.

If you or a loved one has metastatic uveal melanoma, talk to your oncologist. Ask if you’re a candidate for tebentafusp. Ask if targeted radiation could be part of your plan.

This case doesn’t promise a cure. But it shows that progress is happening. And that combining treatments in new ways can lead to longer, better lives.

This was a single case. It’s not a controlled study. We can’t prove the combo caused the long-term response. Other factors could have played a role.

More research is needed. Larger studies are required to confirm this effect and find out who benefits most.

Researchers are now planning studies to test this combo in more patients. They’ll look for biomarkers—signs in the blood or tumor that predict who will respond best.

If these studies confirm the benefit, this approach could become a new option for metastatic uveal melanoma. For now, it’s a hopeful sign in a tough disease.

Study Details

Study typeCohort
EvidenceLevel 3
PublishedApr 2026
View Original Abstract ↓
BackgroundUveal melanoma (UM) is a rare intraocular malignancy with limited systemic treatment options and poor outcomes once metastatic. Tebentafusp, an ImmTAC (Immune-mobilizing monoclonal T-cell receptor Against Cancer) targeting gp100 in HLA-A*02:01–positive patients, has improved survival, although durable responses remain uncommon. Radiotherapy (RT) has been shown to induce immunogenic cell death and to modulate antitumor immune responses, supporting a potential synergistic interaction with systemic immunomodulatory therapies.Case presentationWe described a 39-year-old woman with localized UM initially treated with proton therapy (60 Gy in four fractions), who developed liver and hilar adenopathies metastases seven years later. After confirmation of metastatic melanoma and HLA-A*02:01 positivity, tebentafusp was started and well tolerated. Following four months of therapy, imaging revealed oligoprogression in a hilar adenopathy, while hepatic lesions remained stable. Stereotactic body radiotherapy (SBRT; 30 Gy in 10 fractions) was delivered to the nodal site while tebentafusp was continued. Subsequent MRI at nine months demonstrated partial response across all lesions. The patient has maintained disease control for an additional 35 months, with excellent quality of life (ECOG PS 0).ConclusionThis case illustrates a durable systemic response after combined tebentafusp and SBRT, suggesting a synergistic interaction between ImmTAC-mediated T-cell activation and radiation-induced immunogenic modulation. Local RT may enhance antigen release and T-cell recruitment, amplifying tebentafusp efficacy and inducing abscopal-like effects. Prospective studies are warranted to evaluate this combination and identify biomarkers predictive of response.
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