Parallels between Disease States

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November 30, 2016
By Michael Kaplan
MRA President & CEO

Six months ago I was offered the opportunity to serve as President & CEO of MRA and in July, I officially began. For the past 24 years, I’ve worked in the HIV field and am struck by the many parallels that exist between my past work and melanoma.

I’m awed by the opportunity in melanoma treatment. The fact that prior to MRA’s founding in 2007, there were only two FDA approved therapies for the treatment of melanoma astounded me, as did MRA’s drive to accelerate research and its role in advancing the development of 11 new treatments.

It is the expansion of treatments in particular that shines a light on key parallels between melanoma and HIV. In 1992, we had one treatment for HIV and an average life span of less than 10 years. Today, there are over 30 treatments available, and the life span for someone infected extends almost as long as the uninfected. Those advances were not found through one magical treatment, but through a better understanding of how to combine treatments; knowing which treatments might work best for individual patients and when to effectively begin treatment. Likewise, in melanoma, while treatments have advanced and some show great promise, it is the combination of treatments that may deliver the most effective results. A glance at MRA’s research portfolio demonstrates key research we are funding to better understand what combinations are most effective and what biomarkers might exist to indicate selection of treatment while exploring new ideas.

In the world of HIV, as in melanoma, one of the most significant challenges is simply that of early diagnosis. For both, timely detection is critical. With this in mind, MRA funded INFORMED — a curriculum designed to train primary care physicians in the early detection of melanoma. Subsequently, MRA funded research that revealed the capacity of this program to increase early diagnosis, without increasing emotional distress or unwarranted procedures among patients.

Other parallels include the approximate 10,000 lives that melanoma and HIV each take annually in the U.S.; the fact that both have seen immense progress in treatment and the reality that patients will achieve the best health outcomes by ensuring they are well educated on treatment options. Beyond these similarities, this new chapter for me is significant on a personal level. I’ve lived the impact of a stage IV cancer diagnosis and passing of my spouse and known the fear of having a parent diagnosed with melanoma. I know all too well the realities of cancer gone unchecked and the prospect of surviving melanoma through expedited research and early detection.

As these are things that give me a sense of purpose, they also light the way as I take on the role of CEO for MRA. I am honored and excited to serve in this capacity, knowing science has been and will continue to be, the crown jewel of MRA’s efforts to reduce death and suffering due to melanoma. I look forward to not only advancing this science, but to communicating to our donors, patients and constituents the caliber of work being carried out by MRA and our research partners. This e-news is the first of many steps in moving forward on that promise as we grow our regular and ongoing communications efforts.

Uncommon Immunotherapy Side Effects

14863417947_448cda6c97_o-4 Louise M. Perkins, Ph.D.
MRA Chief Science Officer

A recent report in the prestigious New England Journal of Medicine (NEJM), has spawned reports like this one, regarding the risk of death in patients treated with combination checkpoint treatments. The first author of the NEJM story is MRA-funded investigator, Doug Johnson at Vanderbilt.

Melanoma patients who were the main focus of this article experienced immune-mediated cardiac toxicity after treatment with the Ipilimumab/Nivolumab (Ipi/Nivo) combination therapy regimen. What happened? It seems the patients’ immune systems launched an attack against the heart.  While immune side effects are known with checkpoint therapies, this particular one is quite rare and potentially quite serious.

The authors report this complication is observed in just over 0.25% of patients treated with the Ipi/Nivo combination.  How likely is that? It’s a bit more likely than heads coming up in 9 consecutive coin flips.  The data indicate the cardiac toxicity is more common in patients treated with the combo compared to patients receiving Nivo alone, in whom the risk was much lower (0.06%). Overall, 18 cases of cardiac toxicity were reported in just over 20,500 patients treated with either Nivo or Ipi/Nivo, with 6 fatalities.  In a separate report published in August in the Journal for Immunotherapy of Cancer, 8 melanoma patients were described who experienced cardiac toxicity related to treatment with checkpoint inhibitors – either Pembrolizumab, Ipi, or the Ipi/Nivo combo.  It appears that the approved checkpoint inhibitors may have this undesirable and as of yet unpredictable toxicity.  The use of steroids and other immunosuppressants appear to be helpful in some cases for managing side effects, though, unfortunately, not yet for everyone. To put the latest news in broader context, there are other kinds of immune-related side effects that are also potentially fatal, and we were already aware that the Ipi/Nivo combo in melanoma has more side effects than Nivo monotherapy.

While a cause for concern and highlighting the need for better monitoring, it’s important to keep focused on the significant benefit that checkpoint therapy offers many melanoma patients.  As a reminder, for melanoma patients with metastatic melanoma treated with Ipi alone, one in five is alive at 10 years.  For patients treated with anti-PD-1 antibody alone, about one-third will remain alive at 5 years.  Contrast that with the risk of cardiac toxicity of ~0.25% in Ipi/Nivo treated patients.  While there is a lot of work to be done to further improve all of these numbers, there should be no loss of optimism around checkpoint treatments and the benefits they offer for many patients.

It is up to the field to continue furthering the research to develop new, improved treatments while simultaneously working to monitor and manage the unwanted side effects of these agents.

Learn more about immunotherapy side effects here.

Championing Collaboration

Team support

Louise M. Perkins, Ph.D.
MRA Chief Science Officer

Some have the impression that cancer researchers, whether in academia or in industry, toil away in isolation. While there are certainly scientists who work best on their own, collaboration among researchers has become increasingly common, with a goal of achieving the most promising results in the shortest time frame. For MRA, one of our primary objectives is to foster a collaborative research process to further accelerate results for patients. How do we do that? First and foremost, we are able to meet this goal by way of our approach to fostering collaboration via the research we fund.

MRA’s Team Science Award (TSA) Program is the centerpiece of MRA’s research funding portfolio. Multidisciplinary teams consist of Principal Investigators with complementary expertise who may be from the same institution, from different institutions and/or international. Team science projects promote transformational melanoma research advances with the potential for rapid clinical translation. This is a major emphasis in our portfolio of research. Fully 65% of MRA research awards, since our first grant in 2008, have been made to support team science.

Examples of TSAs that we’ve funded include projects led by Suzanne Topalian at Kohn Hopkins and Jedd Wolchok at Memorial Sloan Kettering Cancer Center — to name a few — to catalog the behavior of markers that might be used in the clinic to predict who will or will not respond better to immunotherapy. MRA was among the first to support theses types of studies and the results helped lay the foundation for our understanding of PD-L1 as a biomarker for PD-1 therapies in melanoma and other cancers. In addition, MRA has funded TSA work by Memorial Sloan Kettering’s Neal Rosen on BRAF and its inhibition. This is important research since about half of melanoma patients have a mutated BRAF and these individuals are eligible for several FDA-approved BRAF-inhibitor therapies. Rosen’s research along with that of others has advanced the fundamental understanding of BRAF signaling in melanoma and has informed clinical trials of multiple targeted therapy drugs.

Another program fostering collaboration is MRA’s Academic-Industry Partnership Award program. Designed to facilitate interactions between the academic and industrial research sectors, these were introduced in 2011 and are co-funded by MRA and an industrial collaborator whose involvement is essential to the project. This program is open to individual Established Investigators or Research Teams. Examples of inter-disciplinary research fostered by this program include the program recently funded by MRA and Amgen and led by Yvonne Saenger at Columbia University. Dr. Saenger is studying the oncolytic virus, TVEC, in combination with another cutting edge treatment for melanoma, PD-1 checkpoint blockade.

When it comes to drug development, it’s hard to quantify the direct impact of collaborations. Suffice to say that in many business contexts, high-performing teams have been noted to produce outstanding results. But, is every individual and every project suitable for a team solution? Definitely not. Though, when teams of individuals with complimentary characteristics come together with the right goals, right leadership and right incentives, they can do amazing things.

For example, it seems safe to say that every clinical trial that has led to an approved melanoma therapy is a project involving collaborations between numerous researchers from industry and academia. You just can’t get new drugs to patients without collaboration! And, the FDA’s Breakthrough Therapy designation has allowed for more open discussion between FDA and drug developers of the most promising medicines. In melanoma, there have been some very rapid approvals of Breakthrough Therapy drugs, including both pembrolizumab and nivolumab. So, patients have benefited and will continue to benefit from collaborations, now and into the future.

Collaboration is at MRA’s core — from the team research that we fund, to the way we find partners who can help us realize our vision. MRA’s ability to fund wide-ranging research in melanoma is amplified by unique, multi-faceted collaborations and partnerships with individuals, private foundations and corporations.

MRA Funded Melanoma Researchers Led Discussions at 2016 Annual Meeting of the Society for Immunotherapy of Cancer

By Pamela Goldsmith25319675619_acc52c5f70_b
MRA Director of Communications

Melanoma Research Alliance (MRA) investigators and other melanoma researchers had a significant presence at this year’s annual meeting of the Society for Immunotherapy of Cancer (SITC) held in National Harbor, Maryland. A key forum for scientific exchange and enlightenment in the cancer immunotherapy field, the conference had over 2,700 attendees from across the globe.

More than 15 MRA affiliated scientists delivered findings from their research as featured speakers.

Suzanne L. Topalian, MD, of Johns Hopkins University School of Medicine, Chair of the MRA Scientific Advisory Panel and member of MRA’s Board of Directors was among the group of scientists presenting at the meeting. Dr.Topalian, recipient of the SITC Richard V. Smalley, MD Memorial Award and Lectureship, proffered the Smalley Keynote Address, discussing PD-1 blockade in cancer treatment. She joined the John Hopkins faculty in 2006 as inaugural director of the Melanoma Program in its Kimmel Cancer Center and has been the recipient of numerous honors, including the 2015 David A. Karnofsky Memorial Award and Lecture and the 2016 Taubman Prize awarded for her groundbreaking work in cancer immunotherapy. Her research focuses on manipulating “immune checkpoints” such as PD-1 in cancer therapy and discovering biomarkers predicting clinical outcomes.

MRA has supported immunotherapy research since its formation in 2007, including team science awards to Topalian and her colleagues at John Hopkins. Topalian served as MRA’s first chief science officer. In addition to chairing its Scientific Advisory Panel, she serves on the Medical Advisory Panel and on MRA’s Grant Review Committee that provides scientific, merit-based peer review of research proposals submitted to MRA.

“I’ve been able to carry out research in the laboratory and clinic with support from MRA, an organization that is distinctly focused on fostering groundbreaking research with the potential to bring new effective treatment to patients,” says Topalian. “MRA has played a significant role in making it possible for investigators and physician-scientists to progress as we have in establishing immunotherapy as a modality for treating melanoma and other cancers.”

Dr. Topalian notes that an important part of her MRA funded research focuses on defining how the immune system interacts with melanoma and how to use immunotherapies evermore effectively. She says immunotherapy research is one of the most important areas of investigation in melanoma and has brought several new treatments to the clinic for patients with melanoma just within the past few years.

Melanoma has been a case study for immunotherapy. Data generated by MRA-funded scientists is now benefiting patients with several different types of cancer, including lung, kidney, head and neck and bladder cancers and Hodgkin lymphoma.

In 2014 and 2016, MRA and SITC joined together to fund a Pilot Award and a Young Investigator Award to further MRA and SITC’s shared goals for expanding knowledge of immunotherapy. MRA and SITC furthered their collaboration by delivering educational content to patients and caregivers. In 2015 the two groups, in concert with The Global Resource for Advancing Cancer Education, hosted an Immunotherapy Patient Forum to provide participants the latest findings in immunotherapy to treat melanoma and other cancers.

Learn more about Suzanne Topalian’s work in immunotherapy here.

How Do MRA Research Proposals Get Funded? An Inside Look at the Grantmaking Process

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By Tasheema Prince
MRA Scientific Program Manager

 

It’s 5:01 p.m. on a Friday afternoon in October and the deadline to submit a research proposal for the next slate of MRA funding has officially passed. Researchers have diligently assembled their applications; formatted project descriptions and literature references; gathered letters of support and obtained needed signatures. In just a few months, MRA will announce which proposals will be funded from these submissions.

That’s the overview of the process. But, have you ever wondered about exactly what happens between the time when a research proposal is submitted and the official announcement of awards is made? Here’s an inside look at MRA’s grantmaking process from start to finish.

Summer science planning happens around the same time each year. MRA holds an all-day meeting with Board member and scientific advisor input for the purpose of planning and discussing details of upcoming activities related to the science program. It allows our team to set the framework for MRA’s next Request for Proposals (RFP) that will attract research proposals from scientists and clinicians from around the world.

It’s August and the RFP is announced. On the day the RFP is announced, MRA’s next awards cycle begins and once again sets the stage for MRA’s top priority — funding melanoma research from around the world. For me, it’s exciting to know that soon, many applicants will be logging in to the online application system to share a potentially transformative treatment approach or possibly an innovative way to better prevent, detect and diagnose melanoma.

Proposals are now due. By this time, several weeks have passed since the release of the RFP. Leading up to the due date, I’ll be busy responding to applicant inquiries on a daily basis. Once the deadline finally arrives, I feel anxious and excited to see how many proposals were submitted. In 2016, MRA received nearly 200 proposals from applicants vying for a share of the more than $7 million MRA plans to award. Over the course of a few weeks following submission, the Science Team have their heads down, working through what we call the “Administrative Review,” which is when we check, double-check, and triple check all parts of an application for eligibility and completeness.

The time to finally assign proposals arrives. Based on conflicts of interest, keyword matches, and workload considerations, all submitted applications are assigned to members of our world class, 33 member Grant Review Committee (GRC), comprised of renowned experts in diverse areas of translational cancer research, who then provide scientific review and preliminary scoring.

It’s a new year and all proposals have been scored. This means the reviewers have reviewed their assigned proposals and given preliminary scores based on their overall thoughts. Next, a review of the scoring results determines the cut off for applications that will move forward for final, full review. Unfortunately, this step also results in sending a not so cheery message to applicants whose proposals will not move forward. For those top proposals that will continue in the review, each application is assigned to two GRC members, a primary reviewer and a secondary reviewer, who prepare to present an oral summary and critique to the GRC at an all day meeting. This is held just prior to the start of MRA’s annual scientific retreat.

The Grant Review Committee meeting arrives and aside from dealing with the logistics (i.e., power and internet, table microphones, audio recording system), it’s quite an exciting time, knowing that MRA is one step closer to awarding the next set of promising research proposals. It’s a time when my attention is very much consumed with managing, in real time, conflicts of interests in the room and later compiling a summary of notes from the day’s events.

Finally, it’s time to fund research. In the weeks after the February GRC meeting concludes, the MRA Board of Directors approves of the awards recommended for funding based on a match up of GRC scores and available funding resources.

I’ll then begin to prepare MRA’s latest award letters. As I enter our grant management system and update the status for selected proposals from “submitted” to “awarded,” these researchers now become part of the MRA family. Their critical work in the fight against melanoma proceeds.

To Screen or Not to Screen (for Skin Cancer) – Reframing the Question

July 29, 2016
Louise M. Perkins, Ph.D.
MRA Chief Science Officer

To screen or not to screen actually isn’t the question screen

While an adaptation of Hamlet’s famous phrase may capture the headlines on whole-body skin checks, a deeper dive gets us closer to questions of life and death. In fact, there is no question that skin cancer screening is important!  The real question is when, how and for whom does skin cancer screening fit as a means to protect yourself from the deadliest of skin cancers, melanoma.

Just the facts

An independent body of medical experts called the U.S. Preventive Services Task Force (USPSTF) recently published their findings on the recommendation for whole-body skin examinations for the early detection of skin cancer. With a focus on primary care physicians and the total universe of potential patients, they concluded that there is not enough evidence to weigh the balance of benefits against possible harms in making this a universal practice.

This doesn’t mean screening is ineffective or unimportant for certain individuals – just that the jury is still out on screening for the general population.  Where a clear verdict can be delivered, is the importance of skin checks for those at higher risk for melanoma:  if you have a history of sunburns or UV exposure, family history of skin cancer, more than 50 moles, or fair skin, light eyes and/or red or blonde hair, you should discuss the benefits of regular skin exams with your doctor.  Everyone can use the ABCDE system for a monthly skin check to help identify suspicious moles and bring them to your doctor’s attention.

Here are some more details

What’s new – the 2016 USPSTF recommendation

On July 26, 2016, the USPSTF published a recommendation that there is not sufficient evidence to weigh the benefits of visual skin cancer screening by primary care providers (PCPs) against potential harms for symptom-free individuals who are not at increased risk for melanoma.

That’s a pretty dense sentence so let’s break it down a bit.

Who is the USPSTF?

The USPSTF is a volunteer panel of medical experts who are, despite the name, independent of the U.S. government and provide recommendations about prevention and evidence-based medicine to primary care physicians. This is an influential group whose determinations can have wide-ranging impact on medical practice not only by non-specialist physicians but can also affect health coverage.

What did the USPSTF study?

The task force gathered evidence from the scientific literature to measure if there is enough information of sufficient quality that related to the potential benefit and potential harms of a universal skin screening program.

What is skin screening?

Skin screening involves having a clinician examine the skin for suspicious spots.  A thorough total body exam includes looking on the scalp, between toes, and all points in between.  So, yes, you need to be out of your clothes for it, and it may take you more time to undress and dress for the exam than the exam itself!

What kind of evidence might’ve convinced USPSTF otherwise? Help me understand benefit and harms.

The USPSTF could have recommended that PCPs perform total body skin screens on everyone if robust evidence existed to support it.  A convincing study might have shown that skin screens performed on the general population by PCPs led to decreased deaths from melanoma – and there were not too many biopsies of suspicious lesions that turned out not to be skin cancer – or too much unnecessary anxiety produced by that screening.  At the present time, however, there simply is not enough evidence like this, hence the USPSTF “I” rating for insufficient evidence.

An analogy might be useful here. Broad screening would be like having your mechanic check your car once a year for rust whether or not you have a ding on its body.  With no dings, dents or scratches, the likelihood of rust is next to nil, and the regular checks become just a burden of time and resources; and for the overly anxious person – a bit of non-productive anxiety. Those would be harms. But if your car ran years and years because of this inspection, that would be a benefit. 

So, skin screening is a big waste of time and I should skip it, right?

Wrong. What the USPSTF found is that there’s just not sufficient evidence to recommend for or against PCP screening for the adult general population. However, “insufficient evidence of benefit” is different from “evidence of no benefit.” We know that when caught early, melanoma is highly treatable with surgery. But once it spreads throughout the body (metastasizes), it can be deadly. So, detecting melanoma at its earliest stages is very important. Keep in mind that adults with concerning skin symptoms or who are at higher-risk for skin cancer were not included in the USPSTF’s evaluation. Nor was screening by the skin specialists – the dermatologists – or even skin screening by individuals themselves considered (that evidence will be looked at by USPSTF later).

Um – okay.  So, when it comes to screening, what should I do?

First of all, everyone should check their own skin monthly using the ABCLayout 1DE system. If you’re at higher risk for melanoma, discuss the benefits of regular skin exams with your doctor.  How do you know if you’re at risk? Risk factors include:

  • Fair skin
  • Red or blonde hair
  • Light eyes
  • More than 50 moles
  • History of sunburn or excessive UV exposure
  • Personal or family history of skin cancer
  • Weakened immune system

About half of melanomas are found initially by the patient themselves.  So, for now, take charge of your own skin using the ABCDEs.

If you have something on your skin that looks suspicious, bring it to your doctor’s attention and s/he may refer you for further testing.

What is MRA doing?

The USPSTF conclusion on skin screening means that more research needs to be done on the benefits and potential harms of skin cancer screening. In 2014, MRA funded an interdisciplinary team of researchers to study melanoma skin screening in the primary care setting.  That work is just starting to yield results with a paper published recently.  One of the key components of their approach is a training system that MRA funded in 2009 called INFORMED and is used to teach PCPs skin screening.  We’ve worked with numerous allies to advocate for melanoma awareness and to spread the word that exposure to ultraviolet light (UV) from the sun and tanning beds is the most preventable risk factor for melanoma.

So, learn as much as you can, avoid tanning beds, use sun-safe practices and check your skin and you can decrease your risk of this deadly disease.

Highlights from the National Cancer Moonshot Summit

By Louise Perkins, PhD – MRA Chief Science Officer

National Cancer Moonshot Summit
June 28, 2016
Washington, DC


cancer moonshotThe National Cancer Moonshot was announced by President Obama in his State of the Union Address in January 2016 and VP Biden was charged with spearheading the effort. Few would disagree with Mr. Biden’s selection as leader given the personal experience he and his family endured with the loss of their son, Beau, to cancer. After seeing him speak on the subject at the American Society for Clinical Oncology
meeting, his passion for defeating cancer is very evident as genuine and inspiring. VP Biden continued to convey his passion at the National Cancer Moonshot Summit held two weeks ago in Washington, DC.

This passion is important and widely shared. What’s been gratifying to see is that Mr. Biden has brought in others that share the personal impact, experience, and drive to make a difference.  Greg Simon, the executive director of the Moonshot, was a member of MRA’s Board of Directors, and is a cancer patient himself.  Between the two of them and the Task Force of advisors assembled, the opportunity to propel cancer research forward in new ways is tantalizing.

But passion alone is not enough to exploit available treatments and technology, the potential resources the Moonshot offers, and, importantly, the will to come together to do something different.  Defining the goals of the National Cancer Moonshot and how those will be achieved is critical.

Towards this objective, VP Biden assembled around 300 leaders from around the country to attend the National Cancer Moonshot Summit on June 28 at Howard University in Washington, DC.  It was a privilege to be invited with patients as well as participants from academia, corporations, government and non-profits Hearing the VP and other thoughtful speakers, including emcee Carol Burnett, was a truly inspiring experience.

The overarching objective of the Moonshot is to achieve the work of 10-years in a 5-year timeframe. But how do we get there? 

Moderated working groups were assembled from the Summit participants and tasked to identify the challenges and solutions on topics ranging from improved sharing and harvesting of patient data to increasing the participation of patients in cancer clinical studies. The ideas submitted along with those collected in an online submission tool are to be evaluated by the Task Force as part of the ongoing prioritization of activities to achieve the objective.

What’s next?

We look forward to learning more and participating on behalf of melanoma and all cancer patients to drive towards ever better solutions that speed progress towards improved outcomes.

The Cancer Moonshot is a mission, and all of us #CanServe.