What is the Melanoma Research Alliance?
The Melanoma Research Alliance (MRA) was founded in 2007 by Debra and Leon Black after Debra had been diagnosed with acral melanoma [a rare type of melanoma that forms on the hands or feet]. She was really surprised to learn that there were only two treatments approved by the FDA [Food and Drug Administration], and they had been there for decades: Nothing new was happening. The five-year survival was anywhere from 5% to 15%.
After Debra had taken care of her immediate medical needs, she and Leon were challenged by their friend Michael Milken to set up a foundation to accelerate research for treating melanoma. We are a 501(c)3 nonprofit working to accelerate the science related to the prevention, detection and treatment of melanoma. We did our first grants in 2008, and since then, MRA has granted out a total of $110 million to research, funding 300 different research projects across 144 different institutions within 18 different countries. And out of that, about 90% of it has been spent on advancing treatment.
Since Debra’s diagnosis, there have been 12 new treatments approved for melanoma, and all 12 have been touched by research dollars from MRA. So MRA continues today, granting about $10 million per year. While we’ve seen immense progress, and we’re seeing five-year survival rates closer to 50%, we still know that some of the newest therapies—checkpoint immunotherapies—still don’t work for close to 50% of patients. So we’ve had immense progress, but there’s still a big push for patients who aren’t cured or treated well through the available treatments.
How do you choose the projects to fund?
We use a peer-review selection process. Once a year, MRA puts out a request for proposals, and then we go through a two-tiered peer-review process. The first review has two peers assigned, and if they score it high enough, it then goes to full panel review. The members of our peer-review or grant-review council are on our website, and it’s really the all-stars across many aspects of medical research, from dermatology to pathology, from immunology to general oncology to surgery, radiation and prevention. We try to encapsulate all the expertise across our grant-review panels to be able to look at any proposal received.
Can you tell us about a particularly interesting project that got results?
I think where we were an early funder of something that had an impact way outscaled to what we could ever hope—and way beyond melanoma—would be our investment in checkpoint immunotherapy. In fact, one member of our scientific advisory panel and a very early funded researcher, Jim Allison, received the Nobel Prize in 2018 for his work on checkpoint immunotherapy.
The idea of immunotherapy had been studied for decades, but it hadn’t really been proven, and melanoma is one of the most immunogenic cancers out there. So there is a signal that maybe we can get the immune system to do the job we need in conquering cancer. Checkpoint immunotherapies were first tested, proven and then approved for melanoma. In 2013, Science magazine’s Scientific Breakthrough of the Year was cancer immunotherapy. As of now, immunotherapies have been approved for treating more than 15 different types of cancer, but it was first tested, proven and approved in the melanoma space.
What are some other noteworthy areas of research that MRA is supporting?
We have a challenge in the U.S.: early detection. When caught early, the survival rates for melanoma are well over 95%. The problem is, we often don’t find things early. So we funded a researcher who developed a curriculum to train primary care physicians to more accurately and routinely do skin checks. It’s called the INFORMED [INternet curriculum FOR Melanoma Early Detection] program and is now being used at two medical schools. We’ve also funded research on full-body dermatology scanning at Memorial Sloan Kettering.
This year, we decided to dedicate at least $1 million to funding awards in the areas of artificial intelligence (AI). We came up with five projects. AI has a lot of potential, whether it’s about creating smarter programs that can visually determine whether a lesion is melanoma or just a mole, or look at a pathology slide to figure out risk.
A new area that I find exciting is the microbiome. The microbiome is all the billions of microbes that live on and in a human body—bacteria, things in your gut, things on your skin. And in the last couple of years one of the hot funding areas has become the impact of the gut microbiome on the effectiveness of treatment. There is a lot of work still to be done in this area, there’s a lot still to understand, but there have been major advances in major publications over the last year or two in understanding the microbiome and its influence in immunotherapy.
Let’s talk about the future of research and treatment.
We’re seeing a lot of research interest in combination therapy. It’s similar to early research in HIV. Back in 1992, the only treatment we had for HIV was AZT, and that was pretty toxic; it wasn’t until ’95, when they got the cocktail, the highly active antiretroviral treatment, and the idea of combining treatments—that made a real impact on turning around the trend on death in HIV.
Similarly, we’re in a place now where we know we have a couple of single or double agents, like the BRAF and MEK inhibitors, where we think, Can we combine an immunotherapy and a targeted therapy? The new hot area is further combinations. For example, there are clinical trials combining checkpoint immunotherapies with BRAF and MEK inhibitors in a triplet approach. Others are trying sequencing, and others are trying a whole variety of other kinds of combinations. What we are seeing is those combos often come with more adverse events but sometimes with better efficacy as well—though not always. That said, I think there is a lot of hope in how we combined treatments for best outcome. The trick is trying to figure out the right balance to make sure the adverse events and side effects are tolerable but deliver effective treatment. And what are the right treatments for the right patients?
Research is moving to looking at whether we can start to treat earlier. Historically, you only treated late-stage metastatic melanoma, which would be a late Stage III or IV. Then we got to the idea of adjuvant therapies—after surgery but before recurrence. We’re now moving, as they’ve done in breast cancer, to the idea of neoadjuvant. Can you treat before surgery to reduce the size of the tumor and offer better health outcomes in the long run? Slowly, research is expanding the number of items tested, looking at more combinations. We’re also trying to get earlier in the life stage of the cancer, to see if we can have a greater impact.
For MRA today, and for the three years I’ve been here, each year our panel finds more that warrants funding than we have dollars to award. And so part of that challenge is: How much can we fund? And how do you pick which one? And what has the promise, and are you exploring every place? Our primary focus has been: There are not any good treatment options; let us move that space. And I feel that MRA has done that, along with many other players.
What we haven’t done well in the U.S. is the prevention and detection effort. We’ve seen greater success and know that greater success is doable, as shown in Australia where they’ve been very aggressive in their prevention efforts. It’s one of the few places that has actually turned the trend on new melanoma. And so we’re starting to ask what more we can do on early detection and prevention. For the first time this year, we’re issuing fellows awards for dermatology, those who are either postdoc or residents, to get engaged earlier in melanoma detection and prevention.
MRA has been very active in supporting clinical trials on melanoma. Why is this so important? What are you doing to make clinical trials more accessible to people with melanoma?
Today there are more than 500 different clinical trials open for melanoma. It’s an explosion. But there’s a challenge there, because in the U.S. only 3% to 5% of cancer patients ever avail themselves of the clinical trials.
The only way you get new treatments approved is by trying them in clinical trials. Sometimes the best treatment available may be one that’s in a clinical trial and has yet to be approved by the FDA. And for the patient community, the best way to give back is by being involved in clinical trials that have further research for all treatments.
Clearly, we have more clinical trials than we have the ability to enroll right now, in terms of patients. And so the challenge is: How do we accelerate that? MRA set a three-pronged approach to this. The first was, we wanted a place where patients could go and talk to other patients about clinical trials, about clinical research and that experience. And so we’ve partnered with an online patient community called Inspire to create the Melanoma>Exchange. It’s probably about a 1,200-person community with four moderators, three of whom were diagnosed with late-stage melanoma and who are here today because of clinical trials, and one who is the mother of a pediatric [melanoma patient]. And so we created a space where people could openly discuss issues and ask questions about clinical trials.
Prong two: We wanted to make it easier for people to find clinical trials. ClinicalTrials.gov, which is where all clinical trials in the U.S. need to be registered, is not the most patient-friendly website, and it can be hard to navigate. And so we partnered with a group called Antidote to create our trial navigator, which is accessible on our website. It will ask you questions such as “How far are you willing to travel?” “What is your gender?” “What stage melanoma?” And you never have to give your name or your email or anything, but the more questions you answer, the further it will refine the list of clinical trials that might be right for you. And at the end of that process, the patient gets the number of trials that would be right for them. Which is really making the navigation easier.
The third prong is the effort to up clinical trial participation, our Fight Back Give Back campaign. Cody Barnett, our director of communications, has worked with several patients who’ve gone through clinical trials, and also with researchers and scientists, to flesh out messaging, patient stories and frequently asked questions about clinical trials. The idea of “fight back” is: Sometimes your best option is one not yet approved by the FDA, so look at clinical trials. And “give back” in that you can only advance this for others by being in a clinical trial. We’ve also worked with some of our funded cancer centers that are using some of our social media messaging to raise awareness for clinical trials. We launched Fight Back Give Back at the end of February 2019, and at that point, I think we were getting about 200 unique visitors a month to the trial navigator. And I think we’re up to about 1,000 a month today.
We believe that every patient should be aware of clinical trials as an option. That does not mean there is a clinical trial that’s right for every patient. But look at what your options are. There are some patients who might have no need for a clinical trial: The melanoma was caught early; there aren’t treatments needed at this point. There are others who are maybe doing fine with the approved treatments. You’ve got to work with your doctor to get input and advice, to understand your own body, your own biomarkers and what makes sense for you. But 100% of patients should know that clinical trials are one option and should explore them along with approved treatments as they make decisions on their care in consultation with their doctor.
How can people get involved in MRA’s mission?
While we are the largest nonprofit funder of melanoma research in the world, we are small in footprint. We don’t do the research—we fund it. One hundred percent of donations to MRA go directly to research. Debra and Leon Black cover 100% of the administrative, development and staffing costs. And so we guarantee that anyone donating to MRA, all of their donation will go directly to research.
The most important thing I would say, for everyone, is to be aware, and take action. Know the risks. Is there a history of melanoma in your family? Are you at higher risk because you are fair-skinned or red-haired—though certainly darker-skinned people can get melanoma as well. Do you have lots of moles? If you are at higher risk with those factors, make sure you go see a dermatologist once a year for a full-body skin check, and once a month check your own skin and see if anything looks funny. If a mole looks atypical, whether the border or the diameter or the color, [have it checked out]. So that’s something everyone can do, and partners can check on their partners.
The other is sun safety: Melanoma is one of the most environmentally driven cancers, particularly cutaneous [skin] melanoma. And that’s UV damage, through and through. And so sunscreens, avoiding peak sun hours, using sun-protective clothing, trying to stay in shade—all those are other things people can do as well, in terms of their own risks and helping loved ones.
To learn more about melanoma, see Cancer Health’s Melanoma Basics, Jamie Troil Goldfarb’s Melanoma Diary and our summer 2019 cover story, “I Don’t Have ‘Quit’ in Me”. For more information about the Melanoma Research Alliance, visit curemelanoma.org and MRA’s blog.