On February 16 the FDA announced the approval of TIL therapy or AMTAGVI the first cellular therapy indicated for the treatment of adult patients with cutaneous (skin) melanoma that is unable to be removed with surgery (unresectable) or has spread to other parts of the body (metastatic) that previously has been treated with other therapies.

Since 2011, 16 drugs have been FDA approved that can be used singly or in combination to treat 31 melanoma indications in adult and pediatric patients, including two drugs approved specifically for metastatic uveal (eye) melanoma.  While work remains to improve long term survival rates in subpopulations of melanoma patients, these drugs have increased the survival rate for metastatic cutaneous (skin) melanoma patients by nearly 50%.  

For more information about the FDA approval of TIL therapy or AMTAGVI, view the announcement press release.  

“Being a caregiver is hard, and it’s not something you sign up for. It’s full of complex emotions, both in times of difficulty for the person you are caring for and in times of joy. It can seem very isolating and lonely. 

My wife’s diagnosis came two days before I had been planning to propose to her. I went ahead with the engagement as she was still the girl I wanted to marry. I knew, as I got down on one knee, that I couldn’t be sure what the future would bring us.  

Throughout her many treatments, which ranged from clinical trials from Memorial Sloan Kettering to University of Colorado to UPMC-Pittsburgh and FDA approved therapies, we got married, took a honeymoon, rescued a dog, built a house, and laughed a lot.  

During Katie’s most recent clinical trial, I remember walking back and forth to the hospital from my dimly lit accommodation, in a city that was totally unfamiliar to me, as she lay in the hospital for three weeks. Some days, when she wasn’t feeling well, we only communicated for brief moments. On my walks, I reflected. Had I done enough that day? Did I show up as my best self? What might tomorrow bring for us as the world around us continues to go about their lives. 

In most cases as a caregiver, people see right through you and very rarely acknowledge you (even if they do happen to see you). I get it. In a hospital, a doctor and nurse’s job is to care for the patient first. You have to accept this and do the best you can to continue to show up as the best version of yourself. 

Often when people are very kind to you and do see you, it comes with guilt. Very generous friends and family would Venmo me money for a beer in support. I’d beat myself up over how I spent that money. The internal monologue didn’t stop; it continued to haunt me everyday with the ‘what if‘ scenarios playing backwards and forwards in my mind.  

But I’ve come to realize that to look after my wife, I had to look after myself first. I had to allow myself to feel and I needed to be okay with my emotions, as difficult as it was for me – I am British after all (keep calm and carry on!). I had to let go of control in what was an incredibly difficult situation and step back and realize what it meant to do the best for us in that moment. I learned to introduce myself to doctors and nurses to allow them to bring me into the conversation, which enhanced my comfort. I learned to balance my wellness and be kind to myself, while also letting others help me. For me, this was the hardest thing.  

Throughout the three weeks we spent in Pittsburgh, I knew that I could sit with Katie day in and day out. But that wouldn’t do either of us any good. As her caregiver I wanted to be there at all times to ensure she was being cared for and to talk to her for the brief moments in between her incessant naps. But it was physically and mentally draining. I needed to balance visiting her but also looking after my wellness. I couldn’t look after her if I was not looking after myself first. As a result, I committed to doing something for myself every day. I stretched and ran nearly every morning, explored the city by renting a bike, and enjoyed trying new coffee shops. These moments energized me to continue to show up for her and care for her.  

So when I meet another caregiver, especially one new to the role, I share this advice: be kind to yourself, honor your emotions (even the ugly ones), and before you think about taking care of them, ensure you are giving yourself the grace to prioritize your wellness first.”

Lindsay, an OM thriver, has an uncanny ability to find silver linings in life’s darkest clouds. Her unwavering spirit was put to the test when she received the devastating news that her cancer had spread to her liver. However, amidst the storm, a glimmer of hope emerged: the first FDA-approved treatment for OM had just become a reality. But, here’s the catch – only 50% of OM patients meet the criteria for this groundbreaking therapy. The other half, like Lindsay, are left navigating the labyrinth of clinical trials and experimental treatments, clinging to the hope of finding a life-extending solution.

Yet, Lindsay and her family chose to focus not on the hurdles they faced but on the boundless possibilities that lay ahead. In Lindsay’s own words, “with options comes hope.” Thus, the “Options Bring Hope” research grant, dedicated to Lindsay Zubeck, was born. Its primary goal was to propel research efforts aimed at advancing treatment options for all patients grappling with metastatic uveal melanoma.

For the past two years, the Millers hosted the “Options Bring Hope” fundraiser at Chicken N Pickle in Kansas City. Friends and family eagerly gathered, forming a united front to bolster this noble cause. In this short span, they managed to raise a staggering $300,000 in support of the grant. Together, they carved a path towards a brighter future for the OM community, leaving an indelible mark on the landscape of melanoma research.

The event was nothing short of spectacular; tickets sold out swiftly, and the room (and pickle ball courts) buzzed with an atmosphere charged with passion and love. It was a testament to the power of collective action. The Millers were overwhelmed by the outpouring of love and support from friends, family, and the entire OM community. In their relentless pursuit of hope, they had become a beacon of inspiration, illuminating the path for countless others affected by this rare and relentless disease.

On August 25, Iovance Biotherapeutics Inc. announced the initiation of a rolling Biologics License Application (BLA) submission to the U.S. Food and Drug Administration for TIL therapy for patients with advanced unresectable or metastatic melanoma. A rolling BLA submission helps expedite the FDA approval process by allowing the company to submit information in pieces for review. Progress towards new treatments for metastatic melanoma brings hope to the entire melanoma community and the MRF is grateful to the countless patients that participate in clinical trials that help lead to future drug approvals. More information is available in the official Iovance press release.

The FDA has issued a response to our advocacy efforts, expressly stating that “the proposed rulemaking continues to be a priority for both the Agency and the administration, and it is currently listed as part of the administration’s Unified Agenda with a target date for a final rule in May 2022.” In a follow-up letter this week, the MRF and more than 20 members of the NCSCP applauded the FDA’s commitment to finalizing the rules and ensuring that those in all 50 states are better informed about, and better protected from, the known dangers of tanning beds.

To read the NCSCP letter in full, click here.

The MRF has been strongly committed to ensuring the patient perspective is closely involved in the development of new treatments, creating new educational resources and advocating at the FDA and beyond for greater access and the need for new FDA-approved treatments.

• View the official press release from Immunocore, including quotes from MRF CEO Kyleigh LiPira, MBA and CURE Ocular Melanoma (CURE OM) Co-Founder and Director Sara Selig, MD, MPH.
• Read a recent guest blog post on how this could change the direction of OM research by Keith T. Flaherty, MD, Associate Professor of Medicine at Harvard Medical School, Director of Developmental Therapeutics at Massachusetts General Hospital Cancer Center and Co-Chair of the MRF’s CURE OM Scientific Steering Committee
• Watch the recording from a live Q&A with Marlana Orloff, MD, Associate Professor of Medical Oncology at Sidney Kimmel Cancer Center and Sara Selig, MD, MPH, Co-Founder and Director of CURE OM. Dr. Orloff and Dr. Selig gave an overview of how the new treatment works and answered questions from viewers during the Facebook Live broadcast on February 11, 2022.
• Learn about Samantha’s journey from her OM diagnosis in 2011 to joining a community of “hope seekers” and becoming a dedicated supporter of the OM community, including advocating at the first FDA listening session for advancing the development of new OM treatments like Kimmtrak.

For more information about the MRF’s CURE OM initiative and its work to advance the field of ocular melanoma research, treatment and patient support, visit the CURE OM website or email cureom@melaresearcstg.wpengine.com.

Twenty years ago, we had no therapies that could reliably improve outcomes for patients with any type of melanoma that was beyond the reach of surgery. Uveal melanoma, skin melanoma, all types of melanoma had the same, ominous prognosis once there was evidence of disease spread beyond lymph nodes in the case of other forms of melanoma, or the eye in the case of uveal melanoma. Enrollment in a clinical trial investigating any approach was considered better than pursuing what constituted the available therapies.

Ten years ago, gene expression testing of primary uveal melanomas was validated and introduced as a standard diagnostic test. This method provided phenomenal prediction of who was at very high risk and who was at very low risk of microscopic spread to sites distant from the eye when all other tests showed no evidence of the problem. But, there was nothing that we could offer patients to treat those invisible sites of disease.

In the past ten years, the treatment of skin melanoma that has spread (metastatic) has been revolutionized. Year after year, the percentage of patients with metastatic skin melanoma who were surviving for 5 years and longer climbed by 10% increments. It was an exhilarating time to be in melanoma research. Individual drugs were supplanted by two-drug combinations based on rapidly developing knowledge regarding the basis of success and failure with the first therapies. From 2011, when the first single-drug approaches received FDA approval, combination therapies demonstrated further improvements in outcome, leading to FDA approval of two-drug combinations starting in 2014.

Throughout this decade in which metastatic skin melanoma jumped from being one of the least treatable cancers to the one of the most successfully treated, uveal melanoma outcomes didn’t budge. More than a decade ago, we learned that what makes uveal melanoma tick is fundamentally different than skin melanoma: the genetic mutations that occur in melanocytes in the eye are completely different from those that occur in melanocytes on the skin. And, the ability of the immune system to “see” uveal melanoma was almost non-existent compared to skin melanoma. As a consequence, the drugs that targeted mutations commonly found in skin melanoma were irrelevant for uveal melanoma. And, the drugs that unleashed the immune system to attack skin melanoma rarely produced a similar effect in patients with uveal melanoma.

All of that is changing.

We now have a drug that leads the immune system directly to uveal melanoma cells regardless of where they may have travelled. In a large trial, this drug (tebentafusp, IMCgp100) reduced the risk of dying of uveal melanoma by half compared to any other therapy offered to patients in the other arm of the trial. A notable limitation of this approach is that patients must have a certain “type” of immune system (similar to blood type).

Now our task is clear: use the same approach that allowed us to rapidly move from first generation to second generation drugs; from single-drug approach to combination approaches in skin melanoma. This requires continued research and partnership between patients, melanoma researchers, and companies who have treatments that might build on this monumental first step.

2022 in uveal melanoma feels like 2011 in cutaneous melanoma. Two drugs were FDA approved in that same year; portending the beginning of a revolution that played out over the subsequent years.

Critical advances in ocular melanoma research and treatment development are made possible in part by the dedicated support of the CURE OM community. Learn about the many ways you can participate in the scientific process, and please consider a tax-deductible donation to support this important work:

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As a scientist, a translational researcher and son to a mother who succumbed to cancer, my defining goal is to understand why existing therapies do not cure all cancer patients. My laboratory at the Johns Hopkins University Bloomberg School of Public Health investigates the underlying mechanisms that allow melanoma cells to metastasize and escape therapy, with an emphasis on identifying exploitable cancer cell vulnerabilities that have the potential for clinical translation.

There are an impressive number of FDA-approved therapy options available for melanoma patients consisting of either targeted therapy and/or immunotherapy that initially control and even eliminate the bulk of tumor cells. However, resistance arises frequently due (at least in part) to rare subpopulations of melanoma cells that persist through therapy, metastasize and ultimately regrow with acquired resistance. These “persister cells” are resistant to chemotherapy, targeted therapy and exhibit immune cell-evasive properties making them extremely difficult to kill.

We and others have characterized these aggressive persister cell subpopulations and identify common features including a dormancy-like state that allows long-term survival, high ability to metastasize to distant organs and stem cell-like properties, however it remains poorly understood how to best kill persister cells. In 2019, I received my first independent funding from the Melanoma Research Foundation (MRF) Career Development Award (funded by the Denver and Philadelphia Gala Fund-a-Grants) to experimentally dissect persister cell vulnerabilities that hold the promise to enhance our ability to eliminate the entire tumor and potentially increase the cure rate in patients with advanced disease. Through a novel genetic analysis of melanoma cells and stem cells, our promising preliminary data has identified the g-coupled receptor LPAR1 as a potential Achilles Heel critical for persister cell viability, their metastatic potential and their ability to escape therapy. The funding from the MRF is supporting our lab’s efforts to validate the utility of targeting LPAR1 (as well as downstream YAP1 and mTOR signaling nodes) through “multi-omic” analyses to curb melanoma metastasis and increase the efficacy of existing targeted therapy strategies. Currently, we are investigating the importance of LPAR1 in maintaining the clonal diversity and aggressiveness of persister cell subpopulations using single cell approaches. We believe the insights gained from these studies will become a useful resource for the melanoma research community.

The support of the MRF has also been instrumental in my career development by a) catalyzing my transition into an Assistant Professorship the following year as I launched my independent laboratory and b) sparking multi-institutional collaborations between my group at Johns Hopkins University and researchers with complementary areas of expertise at The Wistar Institute and the University of Pennsylvania. An accomplishment we are proud of that has stemmed from this work are the doctoral and post-doctoral trainees now involved with these studies, with a large number of them being underrepresented minorities in science.

Life-saving advances in melanoma research are made possible by the generosity of supporters like YOU. Please consider a tax-deductible donation today:

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