From immunotherapy to mRNA vaccines – the latest science on melanoma treatment explained

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More than 16,000 Australians will be diagnosed with melanoma each year. Most of these will be caught early, and can be cured by surgery.

However, for patients with advanced or metastatic melanoma, which has spread from the skin to other organs, the outlook was bleak until the advent of targeted therapies (that attack specific cancer traits) and immune therapies (that leverage the immune system). Over the past decade, these treatments have seen a significant climb in the number of advanced melanoma patients surviving for at least five years after diagnosis, from less than 10% in 2011 to around 50% in 2021.

While this is great news, there are still many melanoma patients who cannot be treated effectively with current therapies. Researchers have developed two exciting new therapies that are being evaluated in clinical trials for advanced melanoma patients. Both involve the use of immunotherapy at different times and in different ways.

The first results from these trials are now being shared publicly, offering insight into the future of melanoma treatment.

Svitlana Hulko/Shutterstock

Immunotherapy before surgery

Immunotherapy works by boosting the power of a patient’s immune system to help kill cancer cells. One type of immunotherapy uses something called “immune checkpoint inhibitors”.

Immune cells carry “immune checkpoint” proteins, which control their activity. Cancer cells can interact with these checkpoints to turn off immune cells and hide from the immune system. Immune checkpoint inhibitors block this interaction and help keep the immune system activated to fight the cancer.

Results from an ongoing phase 3 trial using immune checkpoint inhibitors were recently published in the New England Journal of Medicine.

This trial used two types of immune checkpoint inhibitors: nivolumab, which blocks an immune checkpoint called PD-1, and ipilimumab, which blocks CTLA-4.

A woman's arm with a mole on it.
More than 16,000 Australians are diagnosed with melanoma each year. Delovely Pics/Shutterstock

Some 423 patients (including many from Australia) were enrolled in the trial, and participants were randomly assigned to one of two groups.

The first group had surgery to remove their melanoma, and were then given immunotherapy (nivolumab) to help kill any remaining cancer cells. Giving a systemic (whole body) therapy such as immunotherapy after surgery is a standard way of treating melanoma. The second group received immunotherapy first (nivolumab plus ipilimumab) and then underwent surgery. This is a new approach to treating these cancers.

Based on previous observations, the researchers had predicted that giving patients immunotherapy while the whole tumour was still present would activate the tumour-fighting abilities of the patient’s immune system much better than giving it once the tumour had been removed.

Sure enough, 12 months after starting therapy, 83.7% of patients who received immunotherapy before surgery remained cancer-free, compared to 57.2% in the control group who received immunotherapy after surgery.

Based on these results, Australian of the year Georgina Long – who co-led the trial with Christian Blank from The Netherlands Cancer Institute – has suggested this method of immunotherapy before surgery should be considered a new standard of treatment for higher risk stage 3 melanoma. She also said a similar strategy should be evaluated for other cancers.

The promising results of this phase 3 trial suggest we might see this combination treatment being used in Australian hospitals within the next few years.

mRNA vaccines

Another emerging form of melanoma therapy is the post-surgery combination of a different checkpoint inhibitor (pembrolizumab, which blocks PD-1), with a messenger RNA vaccine (mRNA-4157).

While checkpoint inhibitors like pembrolizumab have been around for more than a decade, mRNA vaccines like mRNA-4157 are a newer phenomenon. You might be familiar with mRNA vaccines though, as the biotechnology companies Pfizer-BioNTech and Moderna released COVID vaccines based on mRNA technology.

mRNA-4157 works basically the same way – the mRNA is injected into the patient and produces antigens, which are small proteins that train the body’s immune system to attack a disease (in this case, cancer, and for COVID, the virus).

However, mRNA-4157 is unique – literally. It’s a type of personalised medicine, where the mRNA is created specifically to match a patient’s cancer. First, the patient’s tumour is genetically sequenced to figure out what antigens will best help the immune system to recognise their cancer. Then a patient-specific version of mRNA-4157 is created that produces those antigens.

The latest results of a three-year, phase 2 clinical trial which combined pembrolizumab and mRNA-4157 were announced this past week. Overall, 2.5 years after starting the trial, 74.8% of patients treated with immunotherapy combined with mRNA-4157 post-surgery remained cancer-free, compared to 55.6% of those treated with immunotherapy alone. These were patients who were suffering from high-risk, late-stage forms of melanoma, who generally have poor outcomes.

It’s worth noting these results have not yet been published in peer-reviewed journals. They’re available as company announcements, and were also presented at some cancer conferences in the United States.

Based on the results of this trial, the combination of pembrolizumab and the vaccine progressed to a phase 3 trial in 2023, with the first patients being enrolled in Australia. But the final results of this trial are not expected until 2029.

It is hoped this mRNA-based anti-cancer vaccine will blaze a trail for vaccines targeting other types of cancer, not just melanoma, particularly in combination with checkpoint inhibitors to help stimulate the immune system.

Despite these ongoing advances in melanoma treatment, the best way to fight cancer is still prevention which, in the case of melanoma, means protecting yourself from UV exposure wherever possible.

Sarah Diepstraten, Senior Research Officer, Blood Cells and Blood Cancer Division, WEHI (Walter and Eliza Hall Institute of Medical Research) and John (Eddie) La Marca, Senior Research Officer, Blood Cells and Blood Cancer, WEHI (Walter and Eliza Hall Institute of Medical Research)

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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  • Women take more antidepressants after divorce than men but that doesn’t mean they’re more depressed

    10almonds is reader-supported. We may, at no cost to you, receive a portion of sales if you purchase a product through a link in this article.

    Research out today from Finland suggests women may find it harder to adjust to later-life divorce and break-ups than men.

    The study used population data from 229,000 Finns aged 50 to 70 who had undergone divorce, relationship break-up or bereavement and tracked their use of antidepressants before and after their relationship ended.

    They found antidepressant use increased in the four years leading to the relationship dissolution in both genders, with women experiencing a more significant increase.

    But it’s too simplistic to say women experience poorer mental health or tend to be less happy after divorce than men.

    Remind me, how common is divorce?

    Just under 50,000 divorces are granted each year in Australia. This has slowly declined since the 1990s.

    More couple are choosing to co-habitate, instead of marry, and the majority of couples live together prior to marriage. Divorce statistics don’t include separations of cohabiting couples, even though they are more likely than married couples to separate.

    Those who divorce are doing so later in life, often after their children grow up. The median age of divorce increased from 45.9 in 2021 to 46.7 in 2022 for men and from 43.0 to 43.7 for women.

    The trend of late divorces also reflects people deciding to marry later in life. The median duration from marriage to divorce in 2022 was around 12.8 years and has remained fairly constant over the past decade.

    Why do couples get divorced?

    Changes in social attitudes towards marriage and relationships mean divorce is now more accepted. People are opting not to be in unhappy marriages, even if there are children involved.

    Instead, they’re turning the focus on marriage quality. This is particularly true for women who have established a career and are financially autonomous.

    Similarly, my research shows it’s particularly important for people to feel their relationship expectations can be fulfilled long term. In addition to relationship quality, participants reported needing trust, open communication, safety and acceptance from their partners.

    Grey divorce” (divorce at age 50 and older) is becoming increasingly common in Western countries, particularly among high-income populations. While factors such as an empty nest, retirement, or poor health are commonly cited predictors of later-in-life divorce, research shows older couples divorce for the same reasons as younger couples.

    What did the new study find?

    The study tracked antidepressant use in Finns aged 50 to 70 for four years before their relationship breakdown and four years after.

    They found antidepressant use increased in the four years leading to the relationship break-up in both genders. The proportion of women taking antidepressants in the lead up to divorce increased by 7%, compared with 5% for men. For de facto separation antidepressant use increased by 6% for women and 3.2% for men.

    Within a year of the break-up, antidepressant use fell back to the level it was 12 months before the break-up. It subsequently remained at that level among the men.

    But it was a different story for women. Their use tailed off only slightly immediately after the relationship breakdown but increased again from the first year onwards.

    Woman sits at the beach
    Women’s antidepressant use increased again.
    sk/Unsplash

    The researchers also looked at antidepressant use after re-partnering. There was a decline in the use of antidepressants for men and women after starting a new relationship. But this decline was short-lived for women.

    But there’s more to the story

    Although this data alone suggest women may find it harder to adjust to later-life divorce and break-ups than men, it’s important to note some nuances in the interpretation of this data.

    For instance, data suggesting women experience depression more often than men is generally based on the rate of diagnoses and antidepressant use, which does not account for undiagnosed and unmedicated people.

    Women are generally more likely to access medical services and thus receive treatment. This is also the case in Australia, where in 2020–2022, 21.6% of women saw a health professional for their mental health, compared with only 12.9% of men.

    Why women might struggle more after separating

    Nevertheless, relationship dissolution can have a significant impact on people’s mental health. This is particularly the case for women with young children and older women.

    So what factors might explain why women might experience greater difficulties after divorce later in life?

    Research investigating the financial consequences of grey divorce in men and women showed women experienced a 45% decline in their standard of living (measured by an income-to-needs ratio), whereas men’s dropped by just 21%. These declines persisted over time for men, and only reversed for women following re-partnering.

    Another qualitative study investigating the lived experiences of heterosexual couples post-grey divorce identified financial worries as a common theme between female participants.

    A female research participant (age 68) said:

    [I am most worried about] the money, [and] what I’m going to do when the little bit of money I have runs out […] I have just enough money to live. And, that’s it, [and if] anything happens I’m up a creek. And Medicare is incredibly expensive […] My biggest expense is medicine.

    Another factor was loneliness. One male research participant (age 54) described he preferred living with his ex-wife, despite not getting along with her, than being by himself:

    It was still [good] knowing that [the] person was there, and now that’s gone.

    Other major complications of later-life divorce are possible issues with inheritance rights and next-of-kin relationships for medical decision-making.

    Separation can be positive

    For some people, divorce or separation can lead to increased happiness and feeling more independent.

    And the mental health impact and emotional distress of a relationship dissolution is something that can be counterattacked with resilience. Resilience to dramatic events built from life experience means older adults often do respond better to emotional distress and might be able to adjust better to divorce than their younger counterparts.The Conversation

    Raquel Peel, Adjunct Senior Lecturer, University of Southern Queensland and Senior Lecturer, RMIT University

    This article is republished from The Conversation under a Creative Commons license. Read the original article.

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  • Your Brain on Art – by Susan Magsamen & Ivy Ross

    10almonds is reader-supported. We may, at no cost to you, receive a portion of sales if you purchase a product through a link in this article.

    The notion of art therapy is popularly considered a little wishy-washy. As it turns out, however, there are thousands of studies showing its effectiveness.

    Nor is this just a matter of self-expression. As authors Magsamen and Ross explore, different kinds of engagement with art can convey different benefits.

    That’s one of the greatest strengths of this book: “this form of engagement with art will give these benefits, according to these studies”

    With benefits ranging from reducing stress and anxiety, to overcoming psychological trauma or physical pain, there’s a lot to be said for art!

    And because the book covers many kinds of art, if you can’t imagine yourself taking paintbrush to canvas, that’s fine too. We learn of the very specific cognitive benefits of coloring in mandalas (yes, really), of sculpting something terrible in clay, or even just of repainting the kitchen, and more. Each thing has its set of benefits.

    The book’s main goal is to encourage the reader to cultivate what the authors call an aesthetic mindset, which involves four key attributes:

    • a high level of curiosity
    • a love of playful, open-ended exploration
    • a keen sensory awareness
    • a drive to engage in creative activities

    And, that latter? It’s as a maker and/or a beholder. We learn about what we can gain just by engaging with art that someone else made, too.

    Bottom line: come for the evidence-based cognitive benefits; stay for the childlike wonder of the universe. If you already love art, or have thought it’s just “not for you”, then this book is for you.

    Click here to check out Your Brain On Art, and open up whole new worlds of experience!

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  • Butter vs Ghee – Which is Healthier?

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    Our Verdict

    When comparing butter to ghee, we picked the butter.

    Why?

    Assuming a comparable source for each—e.g. butter from grass-fed cows, or ghee made from butter from grass-fed cows—both have a mostly comparable nutritional profile.

    Note: the above is not a safe assumption to make in the US, unless you’re paying attention. Grass-fed cows are not the norm in the US, so it’s something that has to be checked for. On the other hand, ghee is usually imported, and grass-fed cows are the norm in most of the rest of the world, including the countries that export ghee the most. So if “buying blind”, ghee will be the safer bet. However, checking labels can overcome this.

    Many of the Internet-popular health claims for ghee are exaggerated. For example, yes it contains butyrate… But at 1% or less. You’d be better off getting your butyrate from fibrous fruit and vegetables. Yes it contains medium-chain triglycerides (that’s also good), but in trace amounts. It even has conjugated linoleic acid, but you guessed it, the dose is insignificant.

    Meanwhile, both butter and ghee contain heart-unhealthy animal-based saturated fats (which are usually worse for the health than some, but not all, of their plant-based equivalents). However…

    • A tablespoon of butter contains about 7 grams of saturated fat
    • A tablespoon of ghee contains about 9 grams of saturated fat

    So, in this case, “ghee is basically butter, but purer” becomes a bad thing (and the deciding factor between the two).

    There is one reason to choose butter over ghee, but it’s not health-related—it simply has a higher smoke point, as is often the case for fats that have been more processed compared to fats that have been less processed.

    In short: either can be used in moderation, but even 2 tbsp of butter are taking an average person (because it depends on your metabolism, so we’ll say average) to the daily limit for saturated fats already, so we recommend to go easy even on that.

    Want to know more?

    Take care!

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  • Barley Malt Flour vs chickpea flour – Which is Healthier?

    10almonds is reader-supported. We may, at no cost to you, receive a portion of sales if you purchase a product through a link in this article.

    Our Verdict

    When comparing barley malt flour to chickpea flour, we picked the chickpea.

    Why?

    First, some notes:

    About chickpea flour: this is also called besan flour, gram flour, and garbanzo bean flour; they are all literally the same thing by different names, and are all flour made from ground chickpeas.

    About barley malt flour: barley is a true grain, and does contain gluten. We’re not going to factor that into today’s decision, but if you are avoiding gluten, avoid barley. As for “malt”; malting grains means putting them in an environment (with appropriate temperature and humidity) that they can begin germination, and then drying them with hot air to stop the germination process from continuing, so that we still have grains to make flour out of, and not little green sprouting plants. It improves the nutritional qualities and, subjectively, the flavor.

    To avoid repetition, we’re just going to write “barley” instead of “barley malt” now, but it’s still malted.

    Now, let’s begin:

    Looking at the macros first, chickpea flour has 2x the protein and also more fiber, while barley flour has more carbs. An easy win for chickpea flour.

    In the category of vitamins, chickpea flour has more of vitamins A, B1, B5, B9, E, and K, while barley flour has more of vitamins B2, B3, B6, and C. A modest 6:4 victory for chickpea flour.

    When it comes to minerals, things are much more one-sided; chickpea flour has more calcium, copper, iron, magnesium, manganese, phosphorus, potassium, and zinc, while barley flour has more selenium. An overwhelming win for chickpea flour.

    Adding up these three wins for chickpea flour makes for a convincing story in favor of using that where reasonably possible as a flour! It has a slight nutty taste, so you might not want to use it in everything, but it is good for a lot of things.

    Want to learn more?

    You might like to read:

    Take care!

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  • Acid Reflux Diet Cookbook – by Dr. Harmony Reynolds

    10almonds is reader-supported. We may, at no cost to you, receive a portion of sales if you purchase a product through a link in this article.

    Notwithstanding the title, this is far more than just a recipe book. Of course, it is common for health-focused recipe books to begin with a preamble about the science that’s going to be applied, but in this case, the science makes up a larger portion of the book than usual, along with practical tips about how to best implement certain things, at home and when out and about.

    Dr. Reynolds also gives a lot of information about such things as medications that could be having an effect one way or the other, and even other lifestyle factors such as exercise and so forth, and yes, even stress management. Because for many people, what starts as acid reflux can soon become ulcers, and that’s not good.

    The recipes themselves are diverse and fairly simple; they’re written solely with acid reflux in mind and not other health considerations, but they are mostly heathy in the generalized sense too.

    The style is straight to the point with zero padding sensationalism, or chit-chat. It can make for a slightly dry read, but let’s face it, nobody is buying this book for its entertainment value.

    Bottom line: if you have been troubled by acid reflux, this book will help you to eat your way safely out of it.

    Click here to check out the Acid Reflux Diet Cookbook, and enjoy!

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  • Healthy Mind In A Healthy Body

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    The 8-minute piece of music “Weightless” by Marconi was created scientifically to lower the heart rate and relax the listener. How did they do it? You can read the British Academy of Sound Therapy’s explanation of the methodology here, but important results of the study were:

    • “Weightless” was able to induce greater relaxation levels than a massage (increase of 6%).
    • “Weightless” also induced an 11% increase in relaxation over all other relaxing music tracks in the study.
    • “Weightless” was also subjectively rated as more relaxing than any other music by all the participants.

    Try it for yourself!

    Click Here If The Embedded Video Doesn’t Load Automatically!

    Isn’t that better? Whenever you’re ready, read on…

    Today we’re going to share a technique for dealing with difficult emotions. The technique is used in Cognitive Behavioral Therapy (CBT), and Dialectical Behavior Therapy (DBT), and it’s called RAIN:

    • Recognizing: ask yourself “what is it that I’m feeling?”, and put a name to it. It could be anger, despair, fear, frustration, anxiety, overwhelm etc.
    • Accepting: “OK, so, I’m feeling ________”. There’s no point in denying it, or being defensive about it, these things won’t help you. For now, just accept it.
    • Investigating: “Why am I feeling ________?” Maybe there is an obvious reason, maybe you need to dig for a reason—or dig deeper for the real reason. Most bad feelings are driven by some sort of fear or insecurity, so that can be a good avenue for examination. Important: your feelings may be rational or irrational. That’s fine. This is a time for investigating, not judging.
    • Non-Identification: not making whatever it is you’re feeling into a part of you. Once you get too attached to “I am jealous”, “I am angry”, “I am sad” etc, it can be difficult to manage something that has become a part of your personality; you’ll defend your jealousy, anger, sadness etc rather than tackle it.

    As a CBT tool, this is something you can do for yourself at any time. It won’t magically solve your problems, but it can stop you from spiralling into a state of crisis, and get you back on a more useful track.

    As a DBT tool, to give this its full strength, ideally now you will communicate what you’re feeling, to somebody you trust, perhaps a partner or friend, for instance.

    Humans are fundamentally social creatures, and we achieve our greatest strengths when we support each other—and that also means sometimes seeking and accepting support!

    Do you have a good technique you’d like to share? Reply to this email and let us know!

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