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Highlights | New treatment innovations

  • Uveal melanoma is a rare cancer that affects eye tissue.
  • Uveal melanoma spreads to other organs, usually the liver, in roughly half of all patients.
  • Intravenous immunotherapy can help shrink tumors in the liver and improve patient outcomes.

Very few patients ever receive an eye cancer diagnosis. But when they do, it’s typically for uveal melanoma, and they often face an uphill battle. This cancer frequently resists treatment, and it can metastasize (spread) through the body.

UW Medicine has joined a select group of research teams nationwide to find a solution. They are testing a new drug and delivery method that could shrink uveal melanoma tumors that have spread to other organs.

Oncologists from the Fred Hutchinson Cancer Center and interventional radiologists from UW Medicine are introducing this new therapeutic approach to local patients in a clinical trial.

“Uveal melanoma is a complicated disease, so we’re taking a multi-pronged, multi-specialty approach to combat it,” says Wayne Monsky, MD, PhD, a vascular and interventional radiologist involved with the clinical trial.

Understanding uveal melanoma

Although uveal melanoma is the most common eye cancer in adults, it’s still very rare. Only around 3,500 Americans receive the diagnosis each year. Ophthalmologists typically detect it as part of a routine eye exam in patients with no symptoms. However, some people experience signs that lead them to seek medical attention:

  • Blurry or changed vision
  • Changes in eyeball position in the eye socket
  • Changes in pupil size or shape
  • Dark spot on the iris (the colored part of the eye)
  • Flashes of light
  • Floaters (spots that drift in and out of your vision)

For most people, uveal melanoma is still restricted to their eyes when they receive a diagnosis.

“However, if not treated in time, or in the case of recurrence, the cancer spreads in approximately 50% of patients,” says Monsky.

The most common spot for the cancer to spread is the liver, where tumors appear for up to 90% of patients who develop metastatic disease.

This unique tendency for liver metastasis makes the liver an attractive target for Monsky and the UW Medicine team, led by medical oncologist Shailender Bhatia, MD.

“Your liver is a filter that cleans your body, so it’s a really rich microenvironment where tumor cells can travel through your circulation and take hold,” Monsky says. “So, we’re investigating whether people can tolerate systemic immunotherapy in addition to liver-directed therapy to fight the spread of uveal melanoma.”

Standard treatment for metastatic uveal melanoma

For the past decade, Monsky has treated this group of patients that have uveal melanoma that has metastasized to the liver with minimally invasive procedures. These techniques deliver cancer medication to their livers through a small spaghetti-sized catheter inserted in the femoral artery, the largest artery in the leg.

By using a dye that makes the tumor visible on angiography — an X-ray that shows the blood vessels — he gets as close to it as possible to inject medication. Then, in a process called immunoembolization, he injects a drug (granulocyte-macrophage colony-stimulating factor) that triggers the patient’s immune system to fight uveal melanoma cancer cells more effectively.

“The drug targets the cancer cells, so the cancer starts to die,” he says. “Plus, we inject an embolic drug that stops or slows the blood supply. So, the tumor is slowly starved of blood, and it starts to break down.”

The new approach

Researchers with biotech company, TriSalus Life Sciences, designed a new study to solve two problems that limit how well current uveal melanoma therapy works. First, cancer can evade the immune system and the natural T cells in the body to fight disease. Second, the embolic and medication injected during standard liver-directed therapy may not distribute well throughout the tumor due to compression by the tumor.

This novel therapy, now being tested at UW Medicine, addresses both problems. The team delivers an investigational drug SD-101 into the liver, which aims at improving the immune responses against the liver tumors, along with the systemically administered immunotherapy drug nivolumab, which aims at helping the body’s immune cells work better by inhibiting the brakes on the immune cells.

“SD-101 works differently from granulocyte-macrophage colony-stimulating factor. It’s a toll-like-receptor agonist, helping a different line of immune cells mature,” Monsky says. “It helps bring the attention of the immune cells in the liver on to the cancer, hence training them to recognize the cancer.”

But SD-101 could fall short of its potential without a better drug delivery system. Fortunately, for years, Monsky and other groups worked to develop approaches with specialized intra-arterial catheters, which can increase the delivery of therapeutics to the tumor. Now called Pressure-Enabled Drug Delivery (PEDD), it increases pressurized flow to the tumors, forcing them to absorb more cancer-fighting medication.

One such catheter has been developed by TriSalus Life Sciences.

“Instead of being like a piece of spaghetti, this catheter is more like the petals of a flower,” Monsky says. “It opens, makes a seal with the blood vessel, and pushes the vessel to expand, giving the opportunity for more pressurized and efficient drug delivery.”

Positive impact on patients

Monsky says the new treatment is working well. According to initial study results, reported by TriSalus Life Science lead investigators, tumors respond best to the lowest SD-101 dose (2 mg) when used with the immunotherapy drug nivolumab. In fact, 81% of patients saw their tumors shrink or remain stable.

But the benefit for patients goes beyond disease improvement, he says. With this new protocol, they have fewer procedures than standard therapy requires. And, although most patients experience fatigue, these liver directed therapies result in less nausea, vomiting and hair loss than typically experienced with cancer treatment.

These outcomes show a new, more efficient treatment for metastatic uveal melanoma could soon be available.

“Currently, there’s no good systemic therapy for these patients. At UW Medicine, we want to offer patients the best available treatments,” Monsky says. “That’s why it’s important to be involved in this trial. We believe it will be the most effective approach available to patients.”