Treatment 'breakthrough' in man with advanced skin cancer

Behind the Headlines

Tuesday May 31 2016

The most common sign of melanoma is the appearance of a new mole or a change in an existing mole

Melanoma can often spread to other parts of the body

"Skin cancer cure hope for millions as major treatment breakthrough sees man's tumours disappear 'completely'," the Daily Mirror reports.

While the headline is premature, the case report it is based on does present interesting findings.

The study involved a man with melanoma – the most serious type of skin cancer – that had spread to other parts of the body.

He was entered into a small trial to try a combination of immunotherapy treatments, which involves stimulating the immune system to detect and kill cancer cells.

The combination of treatments essentially aimed to boost the numbers of T immune cells that could target and kill the melanoma cells.

The researchers gave the man an infusion of T cells, along with an antibody treatment that would also help boost their numbers.

The man's tumours had not responded to the two treatments when given separately, but taken together they diminished the size of the tumours in his chest.

After three years, he'd achieved complete remission – meaning all signs of the cancer had gone. He remains cancer-free five years later, at his latest check-up.

These are promising findings, but are also the results of just one case. Ten people received the same treatment combination as the man, but only he and one other achieved the same remission.

It is hoped that the researchers will build on these findings to find out who may be suitable for this treatment.

However, at this stage, it doesn't offer a "cure hope for millions", as the Daily Mirror states.

Where did the story come from?

The study was carried out by researchers from the Fred Hutchinson Cancer Research Center, the University of Washington, and the Memorial Sloan-Kettering Cancer Center, all in the US.

Funding was provided by the Cancer Research Institute and a "Stand Up To Cancer" Cancer Research Institute Cancer Immunology Dream Team Translational Research Grant.

The study was published in the peer-reviewed Journal of Experimental Medicine.

The lead author of the study serves on the advisory board of Adaptive Biotechnologies, a biotech company whose technology was used in this case.

The Daily Mirror's headline gives rather false hope to the many people and their families affected by this aggressive cancer.

However, the body of the article is generally representative of the study, and does make it clear that the results were found for just one person.

The relative success of the treatment could have been a lot clearer had they mentioned that of the 10 people who received the new treatment combination, just two achieved complete remission.

Without this context, readers might believe the treatment had a higher success rate than was actually the case.

The newspaper does provide a human angle to the story, which is often missing from typically dry case reports.

The man in question just hoped to live a couple of months more so he could see his daughter graduate from college. The success of his treatment meant that he saw her both graduate and get married a few years later.

What kind of research was this?

This case report investigated a combination of cancer treatments in a person with metastatic melanoma who had not responded to the two treatments given individually.

Malignant melanoma is the most aggressive form of skin cancer. Metastatic means that the cancer has already spread to other parts of the body, such as the brain or lungs.

Various treatment options may be tried at this stage, such as chemotherapy, radiotherapy or biological treatments that help the body's own immune system fight the cancer cells – the latter is the focus of this study.

People with metastatic melanoma do not usually have enough tumour-specific immune cells to prevent the cancer progressing.

Progression can be slowed by transfusing T immune cells – or cytotoxic (cell-killing) T lymphocytes (CTLs) – that are able to target the melanoma cells. But complete remission is rare because the transferred T cells don't survive long.

Another option is to give an antibody treatment to block CTL-associated antigen 4 (anti-CTLA4). Blocking this antigen has been shown to boost the numbers of melanoma-specific T cells.

However, complete cancer remission is rare when giving anti-CTLA4 alone, as is giving T cells alone.

This study aimed to combine the two treatments. The researchers aimed to transfuse melanoma-specific CTLs that were first "primed" by a signalling protein called interleukin-21 (IL-21), which would help boost the numbers of these T cells.

These enhanced CTLs were combined with anti-CTLA4 to see if this would help the skin cancer patient.

What did the research involve?

This was the case of a 53-year-old man who first presented with an advanced melanoma on his right thigh that had already spread to his lymph nodes.

Despite surgery followed by immune therapy with interferon alpha, the cancer had spread to other parts of the body (metastasis) four years later.

He first received four cycles of IL-21 and the cancer progressed, then two infusions of melanoma-specific CTLs and more progression.

He then received anti-CTLA4 (ipilimumab), which initially slowed tumour growth, but four months later he had new metastases.

The man was then treated with IL-21-primed melanoma-specific CTLs, immediately followed by a single dose of ipilimumab. He was monitored for adverse events and disease progression.

What were the basic results?

Before treatment, the man had tumour masses in his chest. Twelve weeks after starting the combined treatment, the tumours started to reduce in size.

After three years, he had complete remission as defined by the state of the immune system and any solid tumours, and remained disease-free five years later.

There were no serious adverse events, apart from a transient high temperature and low white cell count at the time of infusions, which is a common side effect of chemotherapy.

However, he did lose the pigment in his eyebrows and eyelashes (vitiligo), which developed at around 12 weeks when the tumour initially reduced in size and persisted five years later.

The single patient described here represents one of 10 people treated on this combination treatment. He was one of two people who achieved ongoing complete remission.

Of the remaining eight, two achieved a partial response, three achieved a stable disease, and three experienced disease progression.   

How did the researchers interpret the results?

The researchers concluded that, "Combining CTLA4 blockade with the transfer of well-characterized, robust antitumor CTLs represents an encouraging strategy to enhance the activity of the adoptively transferred CTL and induce de novo antitumor responses.

"This strategy may hold broad promise for immune checkpoint blockade-resistant melanomas."

Conclusion

This is described as the first case study in humans to have successfully combined these immune treatments.

The results demonstrate that long-term cancer remission was achieved even after the cancer had previously progressed quickly when the person had been given IL-21, CTL and anti-CTLA4 separately.

These seem to be extremely encouraging findings for metastatic melanoma, a cancer with notoriously poor prognosis.

However, before the findings raise too much hope, it must be emphasised that this case report focuses on just one man.

The researchers note he is one of 10 people entered into the trial of this combination treatment, and only one other person received complete remission as well.

This means this treatment combination may not offer the hope of a complete cure for all people who have reached the advanced stages of this aggressive cancer.

It is unclear why these two people responded so positively to treatment, while the other eight did not. However, new treatment possibilities for advanced melanoma are always welcome.

It is hoped that researchers may be able to build on these encouraging results in future trials to find out which people with metastatic melanoma are likely to be suited to this treatment and would benefit the most from it – for example, by looking at characteristics of their cancer, cell profile and previous treatment.

For now, the most important message for malignant melanoma remains that prevention is better than cure.

Though not all cancers can be prevented, you can help reduce your risk of melanoma by ensuring that your skin and eyes are protected from the sun, and avoiding artificial sources of damaging UV rays, such as tanning lamps or beds.

Read more about how to protect your skin from the sun and reduce your risk of getting skin cancer.

Analysis by Bazian. Edited by NHS Choices. Follow NHS Choices on TwitterJoin the Healthy Evidence forum.

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

Skin cancer cure hope for millions as major treatment breakthrough sees man's tumours disappear 'completely'. Daily Mirror, May 31 2016

Links to the science

Chapuis AG, Lee SM, Thompson JA, et al. Combined IL-21–primed polyclonal CTL plus CTLA4 blockade controls refractory metastatic melanoma in a patient. Journal of Experimental Medicine. Published online May 30 2016

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