8th Annual Scientific Retreat Recap

The end of February was a momentous one for the MRA team and all the folks in the melanoma community. We hosted our 8th Annual Scientific Retreat in Washington, DC, and they truly just seem to get better and better.

The Retreat serves two main roles for those invited participants. First, is the centerpiece of scientific knowledge sharing, as evidenced by the more than 20 MRA-funded investigators who presented at the meeting as well as several supplementary events and sessions aimed to provide a holistic look at the state of melanoma research and treatment. Secondly, the Retreat provides an opportunity for participants from all sectors to network. We consistently hear about the new collaborations to fight melanoma that arise from networking at this meeting.

Our Melanoma Forum opened the Retreat with a session about the continuing evolution of patient participation in the research process. It was attended by 50 patients, advocates, and supporters who shared their personal experiences to help advance our work by articulating the unmet needs and burden of the disease from those who understand it personally. Special thanks to Raj Kulkarni, an MRA Young Investigator at UCLA, and Kim McCleary of FasterCures for helping to build out this event.

MRARetreat_Selects-16Our lunchtime panel discussion (left), moderated by Mike Milken, featured four amazing thought leaders in melanoma. Drs. Boris Bastian of UCSF, Levi Garraway of Dana-Farber Cancer Institute, Lynn Schuchter of U Pennsylvania and Suzanne Topalian of Johns Hopkins University wo provided a look forward for the future of melanoma research.

In addition, we convened the growing group of MRA-funded Young Investigators to explore several key issues in clinical translation, while our Industry Roundtable meeting brought together representatives from the NCI, FDA, academia and industry to thoughtfully address challenges and opportunities for future collaboration on behalf of patients.

MRARetreat_Selects-19A highlight of the meeting was welcoming newly appointed FDA Commissioner Robert Califf (left), who came straight from his confirmation at the White House to deliver remarks to the MRA community.

It was truly a convergence of the brightest stars in the field and a community dedicated to achieving MRA’s mission of defeating melanoma. You can read more about in blog posts from Dr. Len, of the American Cancer Society, and T.J. Sharpe, a melanoma survivor who blogs for Philly.com.

We thank everyone who came to participate in the meeting, as well as our sponsors, who all helped make our 8th Annual Scientific Retreat a success!

 

 

Understanding Immunotherapy Part 2: PD-1

By Amrita Bhatt, MRA Intern

Now that we’ve provided a brief background on immunotherapy, it’s time to dive more deeply into the subject. In the second installment of this blog series, we’ll be examining PD-1, a protein that plays a crucial role in cancer’s ability to hide from our immune systems.

What is PD-1?

PD-1 is a protein found on certain immune cells, including a type of white blood cell known as a T cell. When PD-1 links up with its partner protein, PD-L1, a signal is sent to the T cells to shut down. Usually, this is used as a means to prevent the development of out-of-control immune activity that could lead to auto-immune disease. Unfortunately, the same PD-1/PD-L1 signal can be used by tumors to turn off T-cells and thereby help the tumors avoid being destroyed by the immune system.

What anti-PD-1 drugs are available now?

Two anti-PD-1 drugs have been approved by the FDA – Nivolumab (Opdivo®) and Pembrolizumab (Keytruda®). These drugs block PD-1 and free up the T cells to attack the cancer. Additionally, the combination therapy of Nivolumab and Ipilimumab (Yervoy®), an anti-CTLA4 drug, was approved just this past year.  First FDA-approved in melanoma, these anti-PD-1 treatments are also available for kidney and lung cancer patients, and the data are encouraging in a number of other cancers as well.

What type of anti-PD-1 research has MRA funded?

With melanoma serving as the lead for immunotherapy across various cancer types, research funded by MRA has played a pivotal role in advancing the field. Funding from an MRA Team Science Award to Drs. Drew Pardoll, Suzanne Topalian, and Lieping Chen at Johns Hopkins University provided some of the earliest observations on the role of PD-L1 as a potential biomarker in melanoma, lung, and prostate cancer patients. Correlating the expression of PD-L1 to treatment response has contributed to understanding its best use as a biomarker for cancer therapy.

Watch this video to learn more about research on immunotherapy that blocks the PD-1/PD-L1 pathway:

MRA has funded a number of studies on biomarkers for immunotherapy.  In partnership with the Lung Cancer Research Foundation and Lungevity, MRA-funded Young Investigator Dr. Lucia Jilaveanu is conducting research to identify biomarkers that relate to pembolizumab treatment in patients with metastatic brain disease. This partnership allows for powerful insight across cancers, as brain metastasis is a common feature of both melanoma and lung cancer. MRA is also currently funding the melanoma supplement of the SU2C-CRI Immunology Dream Team co-led by Drs. James Allison and Antoni Ribas. Their studies aim to identify biomarkers of response in patients treated with ipilimumab, nivolumab, and a combination of the two.

What’s Next?

With the potential to help combat not only melanoma, but many other types of cancers, anti-PD-1 therapy provides great promise. Melanoma is referred to as the case study for this new wave of cancer therapy, and researchers are now exploring immunotherapy across many cancer types. As MRA-funded researchers continue to study the mechanisms underlying therapy response and resistance, more and more patients will benefit from the knowledge gained.

 

Keep a look out for our next post discussing another protein integral to cancer’s ability to evade our immune systems – CTLA-4.

Understanding Immunotherapy Part 1: What is Immunotherapy?

By Amrita Bhatt, MRA Intern

If you follow science, you have probably heard about immunotherapy. In just the last year or two, immunotherapy has burst into the mainstream media, with coverage from the New York Times to Time Magazine bringing this emerging field to light beyond the scientific community. More recently, President Jimmy Carter helped put a face on immunotherapy when he announced its use in treating his metastatic melanoma.

While there is a broader understanding of immunotherapy now than there was a few years ago, there is a lot to discuss on this complex topic. We’ll be starting a blog series to help readers understand immunotherapy – and how it is being used to treat melanoma and other cancers.

Let’s start with a little background. Just 10 years ago, there were hardly any treatments available for patients diagnosed with melanoma, and a diagnosis of metastatic melanoma was an almost certain death sentence. Since MRA’s founding, the FDA has approved 11 therapies for melanoma. These have included targeted and immunotherapies – and combinations of the two. With nearly $68 million in funding to date, MRA continues to play an integral role in making revolutionary changes available for patients.

So, what is immunotherapy?

It’s a method of treatment that involves engaging the patient’s own immune system to fight cancerous cells. Four of the eleven FDA approved therapies since 2011 have been checkpoint therapies, including one combination therapy, and MRA’s funding has been vital to keeping the momentum going.

How does immunotherapy work?

Our immune system protects us by warding off foreign invaders such as bacteria and viruses. The immune system can also sometimes recognize cancer cells. However, since cancer cells arise from our normal cells, sometimes the cancer just isn’t different enough for the immune system to attack it.

In some cases, even when recognized as foreign, cancers use other strategies to evade the immune response. Immunotherapy works to boost your body’s immune response in order to attack cancer cells and prevent them from evading our defenses.

This video provides a visual explanation for how immunotherapy works.

Figuring out how to engage the immune system to fight cancer has been a goal for many years. MRA has funded a great deal of research in this area, including research on two proteins that allow cancer cells to escape attack from the immune system – PD-1 and CTLA-4.

In this continuing blog series, we’ll explain what these proteins are and how MRA funded researchers are strengthening our understanding of their role in cancer progression and treatment. Immunotherapy is broadening the scope of patient therapies and we must continue to fund vital research that keeps the momentum going.

Daughter Celebrates Her Mom’s Health This Holiday Season

By Hilary Rogers

In this guest post, Hilary Rogers, a member of the Leveraged Finance Fights Melanoma Steering Committee, shares her perspective on her mom’s battle with melanoma.

In the winter of 2012, my family and I found out that our mother’s stage 3 melanoma diagnosis had progressed to her lungs. Even though this was not that long ago, the treatments available at the time only promised to delay the inevitable by a few years at most. On the tails of a wonderful

Rogers family

Author Hilary Rogers, left, and her family.

Thanksgiving and Christmas, it was heartbreaking to imagine it being one of the last holiday seasons that my mother, father, brother, sister and I would all spend together as a family. While I am sure that our parents shared the same fears that my siblings and I did, they were determined to not let melanoma interrupt our family’s future holidays together. They remained positive and researched various clinical trials, and we were thrilled when our mother was admitted into a trial for the new and promising immunotherapy drug, nivolumab.

After only a few months of receiving the treatment, the tumors on our mother’s lungs began to shrink. We were ecstatic when her doctor reported that the tumors were no longer there in the fall of 2014. It has been over a year since we received the incredible news, and we are happy to report that our mom is as healthy as ever.

Through good times and bad over the last three years, our mom continues to be the first one up on Christmas morning as she always has been. Rather than eclipse our family holidays, her fight has brought our family and friends even closer together.

When the FDA approved several of the immunotherapy drugs last year, my family and I were thrilled for the thousands of melanoma patients whose lives were about to potentially change by having access to these groundbreaking drugs.  My family and I are extremely grateful for the work and dedication that go into the research, funding and development of these innovative drugs that have changed the medical landscape, and most importantly, the lives of those affected by melanoma.

What we’ve gone through has brought new awareness to my family and everyone we know. I can’t get into my brother’s car without seeing his SPF 70 sunscreen handy in the center console. My sister and I go to the dermatologist regularly for skin checks. This year we’re even taking a family trip for New Year’s to foggy London rather than some warm beach as we have done in the past.

Most importantly, we as a family understand the risks of this disease, but also the hope that lies in today’s new treatments. It has been our goal and pleasure to spread this awareness to people and families going through what we went through so that their holidays may continue to be happy too.

We would like to thank MRA as well as the researchers, doctors and –above all else – the patients who have enrolled in these groundbreaking trials. Your hard work, dedication and bravery have made it possible for our family as well as countless others to look forward to enjoying many more joyful holidays together in the years to come. For that, we are eternally grateful.

Research Q & A: Dr. Michael Atkins

In the latest blog series, we talked with Dr. Michael Atkins, Deputy Director of the Georgetown-Lombardi Cancer Center at Georgetown University, and a member of the MRA Medical Advisory Panel.

Michael Atkins

How did you get interested in melanoma and your field of research?

I had a couple of high school friends who developed melanoma, including someone who died during high school, so I was aware of the disease. In college, I developed an interest in cell biology and immunology. We knew at that time that soluble/diffusable factors could stimulate the immune system at a distance, but no one understood how it worked. I knew that I was interested in oncology because of my interest in cell biology and immunology and I wanted to be involved with patient care. As an oncologist, you’re always an important part of any patient with cancer’s medical team.

My fellowship in hematology/oncology was right around the time that Interleukin-2 (IL-2) was being investigated at the National Cancer Institute, and I got involved in a laboratory researching immunotherapy. The immunotherapy tended to work best in patients with melanoma. So, I was in the right place at the right time and things just came together.  My research interest in immunotherapy and my clinical and personal interest in melanoma intersected and led me to focus on this area.

Explain how your research is making a difference for people with melanoma.

One of the most surprising and gratifying aspects of my work has been seeing how many patients with melanoma can actually respond to immunotherapy. The identification of the immune checkpoints that dampen the immune response and subsequent successful efforts to block them and restore anti-tumor immunity with checkpoint inhibitors has revolutionized the way we treat advanced melanoma and some other cancers. I am continually impressed at how many patients have immune cells that can recognize and destroy their tumors once re-activated.

Further, our advances in melanoma immunotherapy have paved the way for similar advances in patients with all kinds of cancers, many of which we never dreamed of being responsive to the immune system.

Have there been any recent advances in treatment/your research that are particularly encouraging?

In my mind there are three important areas that the melanoma community is actively researching:

  1. Integrating immune therapy with molecularly targeted therapy. We’re looking at the impact of one treatment on the potential responsiveness of other treatments. What’s the appropriate sequence in patients with tumors bearing a BRAF mutation? Does the sequence make a difference? It’s an important practical question that physicians face every day.
  2. Recent work on checkpoint inhibitors suggests combination checkpoint inhibitors have an advantage over single agents. Studies are showing that patients are experiencing better outcomes if we target the multiple immune checkpoints simultaneously, so combination therapy has to be explored and we have to look at which combinations are most active in particular patients.
  3. Using biomarkers to make treatment recommendations. We’re trying to answer important questions, like who can respond best to combination or single agent therapy, and can you “rescue” patients given single agent after they have been given it if it doesn’t respond?

How has MRA funding helped your work?

We’re trying to better understand how other therapies, like molecularly targeted therapies, affect immune responses in the tumor microenvironment. MRA supports my research related to a clinical trial where we perform serial biopsies on patients’ tumors who are receiving BRAF inhibitor therapy. Our goal is to determine if there is an optimal time to start immune therapy after BRAF inhibitor therapy, and if giving it even makes sense.

Five years ago, median survival for patients with advanced melanoma was still 6-9 months and had remained constant for decades. When MRA stepped on the scene, there were new potential targets – like BRAF, CTLA4 and PD1– that had recently been identified. Funding from the MRA has been critical to expediting our understanding of how to optimally exploit these various targets. As a consequence, there is essentially no median survival for patients with advanced melanoma. We may have been able to get to this position eventually without the MRA, but the MRA support has enabled us to do so at practically light speed.

Immunotherapy Patient Forum: 6 Reasons to Attend

On November 7, the Melanoma Research Alliance is co-hosting a Patient Forum on Immunology with Global Resource for Advancing Cancer Education and the Society for Immunotherapy of Cancer. The event will be held at the National Harbor, near Washington, DC. Online registration is open through October 30.

The Forum will cover important topics for several different cancers, including:

  • Melanoma
  • Leukemia/Lymphoma
  • Lung Cancer
  • Genitourinary Cancers

Here are six reasons to attend the Patient Forum:

  1. Hear the Latest Information. The patient forum coincides with the annual meeting for the Society for Immunotherapy of Cancer, a professional meeting for the leading immunotherapists. You will hear the most up-to-date information and thinking from the leading experts.
  2. Immunotherapy is a Hot Topic for Cancer Treatment. You may have seen some of the news coverage about immunotherapy over the last couple of years. This is your opportunity to hear about the cutting-edge ways we’re using the body’s own immune system to fight cancer.
  3. Meet Other Patients. Patients from up and down the East Coast will be in attendance. You will have the opportunity to share your experience and learn about their journeys.
  4. Interact with some of the Leading Doctors. The presenters are among the leaders in the field of immunology, and they have deep expertise in caring for patients using the most up-to-date therapies. This intimate forum will provide an opportunity to ask questions and interact with some of these top doctors.
  5. Information Tailored to Your Cancer. The forum will provide a terrific overview, as well sessions for each cancer type. These break-out panels that are specific to each cancer type will provide a personalized experience for patients and caregivers.
  6. Arm Yourself with Information. You will come away with answers to important questions about treatment options, as well as some ideas for questions you may want to ask your provider. This session is designed to give patients and caregivers the latest information – and empower them to take an active part in their care.

OK, ready to go? Register today!

And if you’re still not convinced, check out the agenda to see the great speaker line up:

Agenda

Melanoma and the Problem of Drug Resistance

In 2002, researchers discovered a link between mutated BRAF genes and nearly half of all melanoma tumors. Since then, BRAF inhibitors—drugs that target mutated BRAF—have become a leading go-to weapon in the battle against melanoma. Their job is to cut off signals sent by altered BRAF that promote the rapid growth and division of cancer cells.

BRAF Inhibitors and Drug Resistance

Studies show that BRAF inhibitors shrink melanoma tumors faster and better than chemotherapy. Unfortunately, the treatment’s success is short lived. It only takes about six months for cancer cells to figure out how to use alternate pathways to grow and divide once again.

Eventually, melanoma tumors become resistant to the drug’s effects, rendering the treatment essentially useless. This is similar to how skin, ear and respiratory infections can build up resistance to certain overused antibiotics.

Another problem with BRAF inhibitors is that 20 percent of users go on to develop a different type of skin cancer called squamous cell carcinomas. Although this form of skin cancer isn’t as serious as melanoma, they still require removal and treatment.

Combination Treatments for Melanoma: BRAF and MEK Inhibitors

Studies show that combining BRAF inhibitors with another targeted drug, MEK inhibitors, leads to better results.

You might be most familiar with the success of combination therapies to treat AIDS. Over the past two decades, the introduction of a triple cocktail—a combination of three gene-inhibiting drugs—has changed AIDS from being a deadly disease to making it more of a chronic, manageable condition. One goal with melanoma research is to come up with a combination drug therapy that works as well on melanoma.

How are Researchers Combating Drug Resistance?

The Melanoma Research Alliance is helping to fund many of these research projects in the hopes of finding better treatment options with improved outcomes.

  • Several ongoing clinical trials are exploring new drugs and drug combinations.
  • Other studies are looking into whether taking medications intermittently instead of daily might lower the risk of drug resistance.
  • Laboratory tests and clinical trials explore whether drug treatment should continue once cancer progresses to a certain point. Some studies suggest there may be benefits of continuing drug therapy, while other findings suggest otherwise.

Another innovative therapy now available for melanoma is immunotherapy. With this treatment, medications called immune checkpoint inhibitors stimulate the immune system to recognize and destroy cancer cells more effectively.

Studies are currently looking at the effectiveness of combining immunotherapy with other treatments, such as targeted therapies. Researchers also are exploring whether it’s best to start immunotherapy early in the treatment process or after the disease progresses.

Read more about research funded by the Melanoma Research Alliance.Some of this information was presented as part of our 7th Annual Scientific Retreat, which was held in February 2015. You can read about MRA’s Scientific Retreat.