Marlana M. Orloff, MD

What advice do you have for patients and caregivers of those recently diagnosed with uveal melanoma?

Because metastatic uveal melanoma is so rare, it’s very important that patients seek a provider who’s familiar with the treatment landscape.One of the other things patients with uveal melanoma can do when they’re first diagnosed is seek out information provided by patient advocacy organizations.

Now that Kimmtrak [tebentafusp] has been approved for metastatic uveal melanoma, it has really brought to light a lot of the differences between uveal melanoma and skin melanoma, and the need for additional treatments. Specifically, there’s a huge unmet need that remains for patients who are HLA-A*02:01 negative. I’m happy to say that there are a number of ongoing clinical trials looking at new treatment options. Having an FDA-approved therapy has also brought greater awareness to this rare melanoma subtype.

Thank you for joining me to learn about uveal melanoma. We hope you found this 

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Marlana M. Orloff, MD, offers advice for patients who are diagnosed with metastatic uveal melanoma.

Advice for Patients Diagnosed with Metastatic Uveal Melanoma

How is Kimmtrak administered? What can patients expect from treatment? How are adverse events managed?

Kimmtrak [tebentafusp] is a weekly IV [intravenous] infusion. Due to the risk of side effects, specifically cytokine release syndrome, the first three doses have to be given in an extended monitored setting where patients are observed for at least 16 hours. During this time, the patient’s vital signs are monitored very closely as there is a risk for low blood pressure, high fever, and low oxygen. Should these occur, patients are managed appropriately, sometimes with things like IV fluids, medication to get the fever down, and in some scenarios, if severe enough, they may require steroids.

For the majority of patients, adverse effects peak during the first three doses, and after the third dose, patients can be safely transitioned to receive their infusion as an outpatient. Most patients following those first three doses do not experience significant adverse effects. One of the more long-term side effects we see for patients who’ve been on tebentafusp for a long time can be things such as whitening of the hair, eyebrows, eyelashes, and skin, which is called vitiligo.

An expert on uveal melanoma reviews the treatment protocol for tebentafusp, which is approved for the treatment of metastatic disease.

Tebentafusp Treatment Protocol in Metastatic Uveal Melanoma

For patients who are eligible for treatment with Kimmtrak, how does this treatment work?

Kimmtrak [tebentafusp] is a newer type of immunotherapy, also called a T-cell redirector, that acts like a magnet that combines your own immune system, your T cell, and drags it over to a target on the cancer, something called gp100 [glycoprotein 100], and kind of forces them to engage, hopefully allowing the immune system to kill the cancer.

In the clinical trial, they compared Kimmtrak to investigator’s choice, which could have been pembrolizumab, dacarbazine, or ipilimumab. Kimmtrak showed a 1-year overall survival of 73% vs 59% in the comparator group. It was this improvement in overall survival that led to the FDA approval of Kimmtrak.

Due to Kimmtrak’s unique mechanism of action, one of the most common adverse effects we can see is rash. The drug can drag the immune system over to something called gp100, which is on the surface of the tumor but also on melanocytes in the skin causing the rash. One of the other adverse effects that we need to monitor patients very carefully for is something called cytokine release syndrome. This type of syndrome is really due to immune overstimulation, and we can see things such as fever, low blood pressure, and low oxygen. It’s very important that these patients are monitored, at least for the first 16 hours, for the first three doses, to ensure that this syndrome, if it does occur, is managed appropriately.

Marlana M. Orloff, MD, discusses key efficacy data and reviews adverse events seen with tebentafusp in patients with metastatic uveal melanoma.

Efficacy and Safety of Tebentafusp in the Treatment of Metastatic Uveal Melanoma

For patients with metastatic uveal melanoma, what are the treatment options?

Metastatic uveal melanoma is unique in that when patients recur, close to 90% or more recur in their liver. For this reason, when we’re talking with a patient about treatments, we can often talk to them about liver-directed or local regional therapy where we treat just the liver or systemic therapies that treat the whole body. Historically, uveal melanoma has been lumped in with skin melanoma, and the treatments that we’ve used for systemic management and systemic treatment have been skin melanoma treatments. However, we know that uveal melanoma is a very different disease than skin melanoma, and that’s why these treatments often didn’t work very well. It wasn’t until 2022 that we had our first FDA-approved therapy specific for uveal melanoma, a drug called tebentafusp, or Kimmtrak.

How do you choose the best treatment for each patient?

When a patient with metastatic uveal melanoma comes to talk about different treatment options, we look at a few different things to determine what the right next step might be. One of the first things we look at is their HLA [human leukocyte antigen] type. The drug that has been FDA approved for the treatment of metastatic uveal melanoma is restricted to patients who are HLA-A*02:01 positive. This matters because Kimmtrak acts like a magnet to drag the immune system over to the cancer cells. And the way that this drug engages with the patient’s immune system is through something called HLA. So it’s very important that a patient is the right HLA for this drug to work. For patients who are HLA-A*02:01 positive, we may choose Kimmtrak as a treatment choice. For patients who are HLA-A2 negative, we can sometimes look at those liver-directed or regional therapies or clinical trials.

When a patient’s diagnosed with metastatic uveal melanoma, it’s important that they talk to the physician about getting a blood test to determine their HLA type. Because again, knowing your HLA type and knowing if you’re HLA-A*02:01 positive may be the determining factor of whether or not Kimmtrak is a treatment option.

Dr Marlana M. Orloff provides an overview of the treatment landscape for metastatic uveal melanoma.

Marlana M. Orloff, MD

Advice for Patients Diagnosed with Metastatic Uveal Melanoma

Tebentafusp Treatment Protocol in Metastatic Uveal Melanoma

Efficacy and Safety of Tebentafusp in the Treatment of Metastatic Uveal Melanoma

The Metastatic Uveal Melanoma Treatment Landscape

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