Tebentafusp

What is tebentafusp?

Tebentafusp is the first and only treatment approved in the UK to treat patients with unresectable or metastatic uveal melanoma who test positive for HLA-A*02:01 but what does this mean?  Uveal melanoma is a distinct type of melanoma that starts in the eye. Unresectable uveal melanoma is a tumour that cannot be surgically removed and metastatic uveal melanoma is where the melanoma has spread to other parts of the body. The HLA test is a blood test to look at your immune type and, like your blood type, this doesn’t change with time.  It is estimated that about 40-50% of the population are HLA-A*02:01-positive.  If you test positive, tebentafusp may be a potential treatment for you.

To understand more about uveal melanoma see here

Tebentafusp is a new immunotherapy treatment with an action on the immune system that hasn’t been used before. It works as a bridge between the cancer cells and immune cells nearby. It also activates the immune cells so they can attack the cancer.

Tebentafusp HLA Test

Understanding Tebentafusp

To support the information on this page we have worked with Dr. Elaine Vickers to create a video which explains how Tebentafusp works and its use in the treatment of uveal melanoma.

Professor Paul Nathan, Trustee of Melanoma Focus and lead author on the New England Journal of Medicine paper that reported on the trial which led to the license of tebentafusp:

“Metastatic uveal melanoma is a rare, difficult to treat and poor prognosis cancer with limited treatment options. Our patients, their families and my colleagues have waited decades for an approved treatment option that has proven benefits. Today, that changes. I am delighted that the MHRA has licensed tebentafusp for use in the UK.”

What are the potential benefits of tebentafusp treatment?

A recent clinical trial showed that tebentafusp is the first therapy in patients with unresectable or metastatic uveal melanoma to prolong patients’ lives. It is what is called a palliative treatment meaning that it cannot cure patients from their cancer but it can significantly extend the time before their uveal melanoma progresses.

The clinical trial showed that tebentafusp was more effective than pembrolizumab, ipilimumab or dacarbazine, the other treatments it was compared to.

What are the potential side effects of tebentafusp treatment?

In the clinical trial patients generally coped well with any side effects they might have experienced.

The most common side effect in patients who received tebentafusp was a cytokine release syndrome which is a reaction by the immune cells. Symptoms can include fever, chills, low blood pressure, nausea, vomiting, rash, tiredness, headache, and shortness of breath. This reaction typically occurs on the first 3-4 occasions the treatment is administered. All patients are therefore admitted to hospital overnight, for at least the first three infusions. Tebentafusp is also started at a lower dose and increased slowly for the first three doses to help reduce the severity of the cytokine release syndrome.

Skin reactions, including rash and itching, can also be experienced by patients treated with tebentafusp. The skin reactions are generally managed by treatment with antihistamine and steroid creams.

Abnormal liver blood tests can be seen in patients treated with tebentafusp.  Liver blood tests will be taken before starting tebentafusp, and during treatment with tebentafusp.

How is tebentafusp treatment given?

You will receive tebentafusp as an intravenous infusion (i.e. through a vein in the arm) over 15-20 minutes. Treatment is given once every week for as long as your medical team see a benefit with treatment, with manageable side effects.

For the first three infusions of tebentafusp, you will be admitted to the hospital overnight so you can be monitored during the infusion and for at least 16 hours after the infusion is completed.

Most patients then receive the next doses in the outpatient clinic and you will be monitored for a minimum of 30 minutes following each of these infusions.

How can I access tebentafusp treatment?

Tebentafusp has been licensed in the UK to be given as a treatment, however it is currently being reviewed by NICE and the SMC in Scotland. These organisations review all new cancer treatments to decide if they are approved for use.

 

‘Some people worry about having a weekly treatment and the impact that might have on their lives. I travel a long way for my infusion as I am on a trial as it was only available in two hospitals at that time. However, it is a very quick infusion and once I am connected I have a cup of tea and then it’s done, so I would imagine if you were treated in a local oncology department the amount of disruption it would cause to your life after the first three weeks is minimal.

The side effects of the rashes disappeared after 5 to 6 weeks and long term side effects I have experienced are loss of pigmentation to initially my eyelashes, followed by the hair on my head that has gradually lost its pigmentation in patches and perhaps a little fatigue, all of which I have found more than manageable.’

Victoria, Kent

Read Victoria’s full story.

Questions you may have

  • How do I get an HLA-A*02:01 test?
  • How long does it take to get the HLA-A*02:01 test result?
  • Is tebentafusp a treatment option for me?
  • Where is the nearest hospital that offers tebentafusp treatment?
  • How will I be monitored in hospital for side effects?
  • How will I know if the treatment is working?
  • Can I take a break from treatment to go on holiday?
  • Are there clinical trials that are potential options for me?

Relevant References:

Nathan, P; Hassel, J.C; Rutkowski, P; Baurain, J-F; Butler,M.O; Schlaak, M; Sullivan, R.J; Ochsenreither, S; Dummer, R; Kirkwood, J.M; Joshua, A.M; Sacco, J.J; et al. (2021) Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med 2021; 385:1196-1206 https://www.nejm.org/doi/full/10.1056/nejmoa2103485 Accessed 24/10/23

Hassel, J.C; Piperno-Neumann, S; Rutkowski, P; Baurain, J-F; Schlaak, M; Butler,M.O; Sullivan, R.J; Dummer, R; Kirkwood, J.M; Orloff, M; Sacco, J.J; Ochsenreither, S; et al. (2023) Three-Year Overall Survival with Tebentafusp in Metastatic Uveal Melanoma. Epub ahead of print. https://www.nejm.org/doi/full/10.1056/NEJMoa2304753 Accessed 24/10/23