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In 2009, a patient with acute myeloid leukemia (AML) was the first person with cancer to have his or her whole genome sequenced, helping scientists to learn more about the molecular drivers of the disease. Despite the knowledge gained, researchers have struggled to develop therapies that specifically shut down those drivers.

But this year brings hope for patients with AML, with the approvals of several new treatment options, including therapies that target specific molecular mutations. Dr. Gwen Nichols, chief medical officer for the Leukemia & Lymphoma Society (LLS), believes that these targeted therapies are helping to usher in the era of precision medicine in AML. As we recognize Blood Cancer Awareness Month, Dr. Nichols explains the challenges of translating knowledge into treatments and why she is excited about the future of precision medicine in AML.

Dr. Gwen Nichols, chief medical officer for The LLS, is hopeful about the future of precision medicine in AML.

Dr. Gwen Nichols, chief medical officer for The LLS, is hopeful about the future of precision medicine in AML.

Why has treating AML remained a challenge?

“AML is a complex and dynamic disease that really needs a precision medicine approach to treat appropriate patients. Some patients diagnosed with AML will respond to standard chemotherapy regimens, but most will relapse. Chemotherapy targets highly proliferating cells but may be missing the cells that initiated the AML. Those cells remain behind, recover and can cause the disease to come back in AML patients. This is one reason why the five-year survival rate for AML patients remains low at just 27 percent.

Why has it been challenging to develop targeted therapies for AML?

“When the AML genome was sequenced, researchers thought they were going to find single mutations that drive the disease. They believed that if you got rid of this single molecular abnormality, you could get rid of the disease. We have found a few of these mutations in other cancers, such as in the Bcr-Abl tyrosine kinase in chronic myeloid leukemia. But over the last decade, we’ve learned that some cancers, including AML, are more complex and driven by multiple factors. So an effective therapy targeting one mutation won’t be the end of the story because it’s only one piece of the puzzle. As we work toward the future of precision medicine, we need to look at multiple targeted therapies in combination.”

 AML is a complex and dynamic disease that really needs a precision medicine approach to treat appropriate patients.


What type of diagnostics would you like to see to facilitate precision medicine in AML?

“In a perfect world where it costs nothing and can be done rapidly, you would sequence a patient’s genome as frequently and as completely as possible. The targeted sequencing that doctors are doing for AML patients today makes the most sense because that information can help determine diagnosis and prognosis. But I fear that we may be missing valuable information by not sequencing more of our patients’ genomes. We also need to sequence at intervals to make sure the disease has gone away and again when there’s evidence that the disease is coming back. We can’t assume that it’s the same [form of the] disease when it returns.”

How do the clinical trial designs need to change for precision medicine?

“In diseases such as AML, it’s clear that there are subsequent mutations as the disease progresses and that the disease becomes more complex as it evolves. Most therapies are first tested in patients with relapsed or refractory disease, but you cannot expect a targeted agent to be effective when other driving mutations have arisen. This is a recipe for failure. We may be throwing out therapies that could benefit patients because we are testing them at a time when the disease is so complex that there’s little hope for a single therapy to be effective. That’s why the LLS’ Beat AML Master Trial is focused on newly diagnosed AML patients.”

What needs to happen to truly enable precision medicine in AML?

“The last couple of months have been exciting with several new therapies introduced for AML. We are seeing real progress toward that now with this first wave of targeted therapies. With over 700 clinical trials active or recruiting in AML, there is certainly more to come. But the hope would be to have several different therapies available that target all the drivers of AML. These therapies will not be developed on their own. We need to think about the best way to help facilitate the future of precision medicine through novel trial design and combinations.”

For more information on the progress of precision medicine, read “Getting Patients Access to ‘Precision’ Medicine Is Crucial.”

Alan F. List, MD, president and CEO of the Moffitt Cancer Center in Tampa, has made many contributions to hematology. List remains focused on what he has to offer the hematology field, so, last December, when he was recognized with the 2016 Celgene Career Achievement Award, he was humbly grateful.

Alan F. List, MD, president and CEO of the Moffitt Cancer Center in Tampa, was recognized with the 2016 Celgene Career Achievement Award.

Alan F. List, MD, president and CEO of the Moffitt Cancer Center in Tampa, was recognized with the 2016 Celgene Career Achievement Award.

Celgene is committed to supporting investigators who conduct hematology research and has established the Celgene Awards, comprised of the Career Achievement Award, Young Investigator Award, and Future Leaders in Hematology Award to recognize those investigators who have made significant contributions to hematology research. In addition to acknowledging the winners, the recipients’ institutions receive a grant from Celgene to continue efforts in hematology research and education.  An independent selection committee selects the institution based on the submissions received.

As nominations are being accepted for the 2017 Celgene Awards for Clinical Research in Hematology, Dr. List shares what continues to excite him about the hematology field, what he attributes his success to and where he thinks research is headed.

2016 Young Investigator AwardWhat did the recognition of your research through the Celgene 2016 Award mean to you?

“This award is a recognition of all the work that my collaborators and I have done together. Nothing that I have achieved thus far has been the result of one individual. It’s always been a collaborative effort.”

Which of your contributions are you most proud of?

“Three things come to mind. The first is my work in developing a treatment option for MDS. In 2001, I was investigating the role of angiogenesis — the formation of blood vessels — in the bone marrow of MDS patients. That research led me to explore whether existing therapies that slow the growth of blood vessels could stop the disease from getting worse. I applied for a grant and conducted a clinical trial that led to a new treatment option.

“The second is my work on multidrug resistance in MDS and high-risk acute myeloid leukemia (AML). We tested a potential therapy and took it to a phase III trial. That study remains the only one to show a survival benefit in high-risk AML patients.

“The third is my work to help speed up findings for the next generation. At the Moffitt Center, I’ve mentored some very bright researchers.”

2017 Celgene Awards: Nominate a Colleague Today!What inspired you to pursue a career in hematology?

“It seemed that there was so much potential for research in bone marrow-based malignancies such as MDS and AML. Researchers can access the disease directly through a bone marrow aspirate or by simply drawing blood from patients and studying the cells. That’s difficult to do in solid tumors.”

“Also the notion that the hematologist serves as both physician and pathologist creates an ideal opportunity to optimize insight into the disease pathology. You understand the case better than anyone as the physician, so you are more likely to have insights when reading the bone marrow.”

This award is a recognition of all the work that my collaborators and I have done together. Nothing that I have achieved thus far has been the result of one individual.

Celgene 2016 Future Leaders in Hematology AwardsWhat were your biggest career challenges?

“For everyone in research, funding is the greatest challenge. It became an even greater challenge for physician researchers like me in the ‘80s and ‘90s. At that time, the National Institutes of Health (NIH) began prioritizing Ph.D.’s for basic research grants and physicians only for trials. It is a challenge to be a successful physician researcher because you have the demands of patient care on the clinical side, but I’ve always enjoyed both aspects. I’ve been fortunate to have great collaborators that have allowed me to explore my research interests and still care for patients.”

What impact do you hope to make as President and CEO of Moffitt Center?

“We haven’t seen any significant rise in NIH funding for nearly a decade. That has been challenging for research institutions like the Moffitt Cancer Center. My responsibility is to make sure that the institution is financially solvent to pursue our mission of improving cancer care. One way we’re doing that is by partnering with insurers and the Center for Medicare and Medicaid Services as they explore new payment models. We’ve also partnered with pharmaceutical companies that have helped sponsor novel laboratory research.”

What is the future of the hematology field?

“In the past, we have been very linear in our view of science and biology. Research focused on gene mutations over the last ten years has been successful, but we know other factors also play significant roles in cancer. The disease is dynamic and complex, and it’s difficult to understand when we look at one part of the whole system.

“We’ll treat and prevent cancer better when we take a systems biology approach and look at the complete picture of how cancer affects the body, including metabolic and cell signaling networks. Systems biology is going to be critical in furthering our understanding of cancer’s complexities.

“At the same time, for many cancers, we’ve also been treating patients the same way for the past 40 years. If a therapy works, we give patients the highest dose that they can tolerate until it stops working. Then we move onto the next therapy, linearly. In the future, we’re going to see more adaptive therapeutic approaches that are flexible and can change in response to a patient’s tumor at a particular time.”

To learn how to nominate a colleague for the 2017 awards, visit the Celgene Awards for Clinical Research in Hematology website.

2017 Celgene Awards: Nominate a Colleague Today!

Although blood cancers are relatively rare, their root causes may not be so different from those of other cancers. And since blood cancer samples may be more easily accessible than solid tumor samples, it can help research efforts and make excellent models for research.

DR. LOUIS DEGENNARO, PRESIDENT AND CHIEF EXECUTIVE OFFICER OF THE LEUKEMIA & LYMPHOMA SOCIETY, EXPLAINS HOW ADVANCES IN BLOOD CANCER HAVE IMPROVED TREATMENT IN OTHER CANCERS.

DR. LOUIS DEGENNARO, PRESIDENT AND CHIEF EXECUTIVE OFFICER OF THE LEUKEMIA & LYMPHOMA SOCIETY, EXPLAINS HOW ADVANCES IN BLOOD CANCER HAVE IMPROVED TREATMENT IN OTHER CANCERS.

“We’re able to make faster progress in blood cancer because we’re studying the real cancer in the patient,” said Louis DeGennaro, president and CEO of the Leukemia & Lymphoma Society. “When you draw a leukemia patient’s blood sample, you have an exact representation of their cancer. That’s not the case in solid tumors, where you’d have to manipulate and grow the cells in a lab to study them.”

That’s why the LLS is especially focused during Blood Cancer Awareness Month on raising awareness of this second leading cause of cancer death in the United States (behind only lung cancer).

Blood cancer is actually a family of over 140 distinct diseases that affect blood cells, acting as “bullies” within the circulatory and immune systems. These abnormal blood cancer cells typically grow more quickly and survive longer than normal, interfering with the production and functioning of healthy cells.

Like all families, though, blood cancers have their differences. Lymphoma, leukemia, multiple myeloma and myelodysplastic syndromes (MDS), four major types of blood disorders, affect specific cell types in particular neighborhoods of the body. For instance, lymphoma alters white blood cells in the lymphatic system, while multiple myeloma disturbs plasma cells in the bone marrow.

These four diseases branch out into further subtypes. Leukemia comprises acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL); lymphoma includes over 60 different forms. The distinction between all those subtypes lies partly in the specific cell type impacted. But scientists are learning that commonalities are more critical than distinctions.

“When it comes to treating cancer, we’re beginning to understand that the kind of cell affected is not the most important aspect,” DeGennaro said. “It’s the underlying mutations and mechanisms—which are shared by many types of cancer—that matter more.”

For instance, researchers have found mutations in a tumor-suppressor gene called TET2 in multiple blood cancers, suggesting it plays a role in how blood cells are regulated in the body. But even beyond blood cancer, the TET gene family has also been linked to breast, liver, lung, pancreatic and prostate cancers.

Blood Cancer's Family Tree

Their commonalities may mean medical advances in one blood cancer could provide insights into others.

An example is a class of therapies called tyrosine kinase inhibitors (TKIs), which have nearly doubled the five-year survival rate for CML since they were introduced 15 years ago. Today, TKIs have been approved to treat many other diseases, including lung, thyroid, kidney and breast cancers.

Roots of Care: Multiple Myeloma

“Blood cancer research is paying dividends to other cancers and diseases, and that will only continue as we learn more about these diseases,” said DeGennaro.

To learn how you can help the Leukemia & Lymphoma Society in supporting blood cancer research, read “Why I’m Walking in Light The Night® This Year.”

Cancer survives and thrives by working around the body’s natural defenses and turning off the immune system’s roadblocks before it can attack the disease. One way tumor cells flourish is by using the programmed death-1 (PD-1) receptor and programmed death-ligand 1 (PD-L1) pathway to dampen the immune system. Innovative new therapies are now tackling this pathway in an attempt to slow the progression of certain tumors

PD-1 is a “checkpoint,” which immune cells use to determine whether they should attack an enemy, such as a tumor cell or a cell infected with a virus, or shut themselves down. Cancers, though, have found ways to manipulate PD-1. For example, they make high levels of its ligand, PD-L1. So when immune cells approach tumors, they become anesthetized by the PD-L1 and lose their ability to attack.

New immunotherapy research is examining whether antibodies that block the PD-1/PD-L1 pathway can awaken and reactivate immune cells so they can once again kill tumor cells.

PD-1 and PD-L1 antibodies release the brakes on the immune system and can restore its natural antitumor response

There are other therapies designed to work with the immune system to combat cancer, but PD-1 and PD-L1 inhibitors may hold unique potential for some hard-to-treat cancers.

“PD-1 and PD-L1 antibodies release the brakes on the immune system and can restore its natural antitumor response,” said Robert Hershberg, Executive Vice President, Head of Business Development and Global Alliances, at Celgene Corporation,former Chief Scientific Officer and leader of the Immuno-Oncology Center of Excellence. “I think there’s very little doubt now that the future of oncology is inextricably linked to the immune system.”

While targeted therapies effectively shut down just one target within cancer cells, immunotherapy has more widespread effects — working with the body’s immune system as a whole to make it more difficult for the cancer to survive. Early clinical research suggests that a range of solid tumor cancers, including melanoma, lung cancer, bladder cancer, head and neck cancer (among others), respond to immunotherapy. Using sophisticated immune monitoring techniques to determine which patients respond to these immune-targeting agents remains a crucial endeavor at Celgene.

Disrupting the PD-1 checkpoint may also result in an unchecked immune response that may lead to adverse effects for some patients. Researchers are learning how to engineer these therapies to not only be more effective but also minimize molecular interactions that may have undesirable consequences.

Down the road, combination therapy with PD-1 and PD-L1 antibodies could be even more advantageous. “It’s a breakthrough and revolutionary, but really the tip of the iceberg,” Hershberg said.

PETER SCHAFER, EXECUTIVE DIRECTOR OF TRANSLATIONAL MEDICINE AT CELGENE, BELIEVES WE ARE AT A TIPPING POINT WHERE THE COLLECTION OF LUPUS GENETIC RESEARCH IS ABOUT TO GIVE WAY TO NEW THERAPEUTIC APPROACHES.

PETER SCHAFER, EXECUTIVE DIRECTOR OF TRANSLATIONAL MEDICINE AT CELGENE, BELIEVES WE ARE AT A TIPPING POINT WHERE THE COLLECTION OF LUPUS GENETIC RESEARCH IS ABOUT TO GIVE WAY TO NEW THERAPEUTIC APPROACHES.

In the past 50 years, only one new therapy has been developed exclusively for lupus. Meanwhile, patients with this inflammatory disease — in which the body’s immune system attacks its own tissue — continue to combat symptoms like fatigue, joint pain and rashes.

But Peter Schafer, executive director of Translational Medicine at Celgene, believes new genetic research in lupus is finally giving way to new investigational approaches that target mutations driving the disease.

As this year’s Annual European Congress for Rheumatology (EULAR) 2017 gets underway in Madrid, Schafer explains how genetic research is opening up new avenues of research for this difficult-to-treat disease.

How is our growing understanding of the genetic changes underlying lupus influencing the development of new treatments options?

We’re living in an era that’s beyond the sequencing of the human genome. Over the past decade, researchers have identified a multitude of genetic variants linked with particular diseases. Companies are beginning to realize the value of targeting the proteins that are encoded by those genes.

Managing Lupus Remains a Challenge

How has our understanding of genetics evolved over the past decade?

Three years ago, if I told someone that there was a change in a part of a gene that did not include the “recipe” for a protein, they would dismiss that mutation. Now we know that you shouldn’t necessarily ignore it. We’re realizing that other parts of the gene may be doing something else—for instance, controlling the quantity of protein being produced. Sometimes, the most obvious experiments go undone. One example is comparing the amount of a protein being produced in people with a given disease and those without. You may never bother to look if you dismiss that genetic change.

Have researchers found such variants that are believed to contribute to lupus?

Yes. For instance, there are variants in the genes for two proteins, called Ikaros and Aiolos, that help with the development of the immune cells that can cause inflammation. Lupus patients have twice the normal Ikaros levels and four times the normal Aiolos levels.

“Until this year, there had not been a program to evaluate a treatment that is designed specifically to target the genetic drivers of lupus.”

Have therapies that target such mutations linked with lupus been developed?

A few medications exist that target some of the proteins of the identified genes, but they are not approved for treating lupus. Their use in lupus will have to be investigated. Until this year, there had not been a program to evaluate a treatment that is designed specifically to target these potential genetic drivers of lupus.

What makes developing targeted therapies for lupus more challenging than for diseases such as cancer?

Lupus can be a debilitating disease, but the mortality rate isn’t as high as in cancer. As a result, a patient is less likely to be willing to deal with side effects, and their expectation is much higher.

Also, you’re not trying to kill a tumor. Instead, you’re trying to maintain some degree of suppression of the immune system over the long term. Lupus patients don’t use a high dose of treatment for a short period and then stop; they have to keep using their therapy. You want to know how low the dose can be and still be effective, so you don’t put the patient at risk unnecessarily.

High Levels of Ikaros & Aiolos in Lupus

How challenging is it to test the efficacy of treatments for lupus?

Lupus affects so many different tissues, joints and organs. Clinical efficacy measures of a new lupus treatment should evaluate the effectiveness of that treatment across the various organ systems involved in lupus. You’re looking for an improvement in at least some of those symptoms without worsening others.

At this time, lupus patients are being classified by which tissues are affected. But now that we’re looking at the disease from a genetic perspective, we have seen genetic variants in lupus patients regardless of the tissue affected. This finding is shifting our thinking about how to approach a disease like lupus, because if all lupus cases have similar root causes, genetic evaluation is important. Classifying patients solely by their affected organs might not be as useful for treatment purposes.

To learn about how targeted therapies are being explored for other inflammatory diseases, read “Accelerating MS Research Through Teamwork, New Approaches.”

Last month, James Fitzgerald celebrated his wedding day. It was an event that he never thought he would see when he was diagnosed with acute myeloid leukemia (AML) six years ago. He was immediately hospitalized, and his liver and kidneys failed within 24 hours. His doctors put him into a medically-induced coma for a week before starting his treatment, which included an intensive combination of chemotherapy and radiation. It was one of the only treatment options for AML at that time.

But that’s changing for AML patients like Fitzgerald. Therapies that target some of the specific molecular genetic changes in AML are being developed, and that’s making mutational profiling more important than ever. That’s good news for Fitzgerald who is currently in remission but is concerned that his disease may one day come back.

“When I was diagnosed, I didn’t know to ask my doctors about the different molecular mutations or whether that would even make a difference in my treatment,” Fitzgerald said. “It was only after my treatment that I started asking questions and learning about the genetics of AML.”

Spot the Difference in AML

Enabled by breakthroughs in genome sequencing and analysis over the past decade, researchers have learned more about the genetics that drive AML. In 2008, an AML patient was the first cancer patient to have her genome sequenced, enabling researchers to discover 10 molecular mutations related to the disease.

Since then, scientists have identified as many as 80 potentially disease-associated mutations in many genes, including NPM1, FLT3-ITD, IDH2, DNTM3A, KIT, IDH1, and CEBPA. They have now found genetic differences between the 34 subgroups of AML, confirming the idea that not every AML case is the same.

This diversity can make treatment a challenge. But scientists and patients are hopeful that a better understanding of these molecular changes will improve outcomes. That’s particularly good news for a disease that has not seen substantial improvements in 20 years.

I hope doctors start learning more about the mutations in AML and start talking with their patients about the genetics of the disease.

The current standard of treatment — an intense combination of chemotherapy — is not particularly easy for patients to tolerate, something Fitzgerald can attest to. Eventually, he received a bone marrow transplant and has been in remission ever since.

“It certainly wasn’t fun,” said Fitzgerald. “I had a 106-degree fever at one point, and I was in the hospital for three months. It was definitely tough for me, but at least I had that option.”

Given the severity of treatment-related adverse events, the standard treatment regimen is often not prescribed for older or unhealthy patients. So while half of AML patients under age 60 years live five years or longer, only up to 15 percent of older patients, who more often cannot receive intense chemotherapy, reach the same milestone.

Mutational Profiling May Help Inform Therapeutic Decisions

Researchers are turning their focus to develop therapies that target the specific molecular mutations that drive AML. A recent analysis of 200 patients showed that more than 99 percent of patients had at least one mutation associated with the disease.

As new targeted therapies are being explored, an understanding of the underlying mutations in each patient becomes increasingly important for doctors and patients to decide on an appropriate treatment plan. The Leukemia & Lymphoma Society is exploring the possibility of bringing a personalized approach to AML treatment through its Beat AML clinical trial. With such initiatives in progress, molecular profiling is on its way to becoming a standard part of disease classification and treatment for AML patients.

“I hope doctors start learning more about the mutations in AML and start talking with their patients about the genetics of the disease,” said Fitzgerald. “I can only hope AML patients don’t have to go through what I faced in my treatment.”

To learn more about how clinical trials are bringing a precision medicine approach to AML, read “Bring Patients Closer to Personalized AML Treatments.”

 

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DR. RAFAEL BEJAR, AN ASSISTANT PROFESSOR AT THE UNIVERSITY OF CALIFORNIA, SAN DIEGO, BELIEVES THAT RESEARCHERS WILL MAKE SIGNIFICANT PROGRESS IN THE TREATMENT OF MYELODYSPLASTIC SYNDROMES PATIENTS.

DR. RAFAEL BEJAR, AN ASSISTANT PROFESSOR AT THE UNIVERSITY OF CALIFORNIA, SAN DIEGO, BELIEVES THAT RESEARCHERS WILL MAKE SIGNIFICANT PROGRESS IN THE TREATMENT OF MYELODYSPLASTIC SYNDROMES PATIENTS.

For patients with myelodysplastic syndromes (MDS) — bone marrow disorders that affect blood cell production — the early 2000s were a time of advancement, when several new treatment options were approved. But since then, research and treatment advances have been minimal.

Now, as researchers gather for the 2017 International Symposium for Myelodysplastic Syndromes this week, there is renewed hope. With a better understanding of the how the immune system and genetic mutations contribute to the disease, experts believe that new treatments may be around the corner. Dr. Rafael Bejar, an Assistant Professor at the University of California, San Diego, explains why he’s looking forward to this year’s event.

What are some of the challenges in treating MDS?

We’ve been relying on three medications that were approved over 10 years ago. These medications have freed some patients from the need for blood transfusions, improved their blood counts and likely extended their lives. But not everybody responds to these therapies. We need more therapeutic options to treat the disease in different ways. When you have multiple medications to choose from, you can also start profiling patients to predict which treatment is going to be best for them allowing you to further personalize care.

What has made medical advances in MDS so difficult?

MDS is very different than many other cancers. With its elderly and often frail patient population, we have to find medications that are not only effective but also tolerable and safe.

To do this, we must understand the disease better than we do today. MDS cells don’t grow well in the laboratory, making them difficult to study.

What recent advances will be highlighted at this year’s symposium?

One of the fascinating new discoveries in the last few years involves how the innate immune system may be involved in the development of MDS. We have learned that MDS cells create inflammation and thrive in this environment. We may be able to target this particular type of inflammation with medications and therapeutic antibodies in order to make MDS cells more vulnerable. This approach has yet to be thoroughly tested clinically, but the research in this area could provide a rich set of therapeutic targets.

There is also growing interest in how B and T cells, which form our adaptive immune system, might play a role in MDS. Researchers are now exploring various types of immune approaches for the treatment of MDs. This exciting research involves understanding how the immune system reacts to MDS cells.

If we can make this disease more manageable, patients will end up living better lives and dying with MDS and not of MDS.

What are researchers learning about the biology of MDS? How are those insights helping us to treat patients?

We’re using mutations to help identify patients who are more likely to respond to a given therapy. Genetics has begun to tease apart different subsets of MDS with distinct patterns of mutations and important differences in clinical outcomes. For example, patients who have mutations in a gene called SF3B1 tend to do relatively well. But patients who have mutations in TP53 usually have more aggressive disease and an overall poorer prognosis. We‘ve always tailored our treatments to our perceptions of how patients are likely to do with their disease, but now we can use more accurate methods to help predict that prognosis.

Some of the new science is also informing the diagnosis of MDS, correct?

Right now, many people who have unexplained low blood counts are left without a diagnosis. They don’t meet the current diagnostic criteria for MDS. But we’re learning that about 40 percent of these patients have mutations associated with MDS. This data supports adding DNA sequencing and mutation tests to our diagnostic workup for these patients. We may need to expand the umbrella of what we consider MDS to include patients with an MDS-like condition that is likely to progress. And, we may be able to tell those patients without these mutations that they’re likely to do well without treatment.

How optimistic are you that we will see more treatment advances soon?

MDS is certainly an area where there’s a lot in development and a lot to feel hopeful about. However, stem cell transplants currently remain our only potential cure. While advances are making transplants safer and more effective, we’ll still need other treatment options for the majority of patients who cannot receive a stem cell transplant. There are several new targets to explore, including inflammatory cascades, immune checkpoint inhibitors, apoptotic pathways and mutated splicing factors. When we succeed we’ll be attacking the disease from many different angles. With these potential new targets, we are looking to make tremendous progress in how we treat patients. If we can make this disease more manageable, patients will end up living better lives and dying with MDS and not of MDS.

To learn more about this blood disorder, read “What Are Myelodysplastic Syndromes?”

BRUCE BEBO, PH.D., EXECUTIVE VICE PRESIDENT OF RESEARCH AT THE NATIONAL MS SOCIETY, BELIEVES THAT ADVANCES IN MS TREATMENT ARE ENCOURAGING.

BRUCE BEBO, PH.D., EXECUTIVE VICE PRESIDENT OF RESEARCH AT THE NATIONAL MS SOCIETY, BELIEVES THAT ADVANCES IN MS TREATMENT ARE ENCOURAGING.

While treatment for multiple sclerosis (MS) has improved over the past 20 years, there’s still no cure. Most people living with MS have a form of the disease called relapsing-remitting MS (RRMS) with cycles of relapses (when symptoms flare up) followed by periods of remission (times of little or no symptoms). But researchers now better understand the pathways that contribute to MS relapses, and that knowledge is driving the development of new treatments.

During this year’s MS Awareness Month (March), we spoke with Bruce Bebo, Ph.D., executive vice president of Research at the National MS Society, to understand the questions driving MS research today and the progress being made.

The National MS Society is funding more than 300 research projects and invests about $50 million in MS research each year. What are some of the most exciting recent advances?

Advances in repairing the myelin sheath, which protects nerve cells and is destroyed by MS, are encouraging. This approach has tremendous promise to work with immunotherapies to stop the disease from getting worse. MS is an autoimmune disorder in which the body’s immune system attacks and destroys nerve cells; so immunotherapies may ultimately slow down or halt the neurodegeneration in MS. A better understanding of the role of B cells (a type of immune cell) play in this destruction will likely lead to new and improved treatments for this type of MS.

Most of the 2.3 million people worldwide with MS have a type called relapsing-remitting MS (RRMS). What are the big questions that are driving research in RRMS? 

We still don’t know the precise targets that the immune system recognizes in RRMS, the environmental risk factors and triggers or how the estimated 200 genes that have been associated with MS actually contribute to the disease.

How will answering these questions help lead to more effective treatment options for patients with RRMS?

Immunotherapies today often affect immune cells that fight infection as well as those that cause MS. Knowing the targets will allow us to develop more precise therapies that will prevent the immune system from attacking nerve cells but not interfere with fighting infections. Understanding the environmental lifestyle factors and genetic factors will also reveal pathways and strategies for treatment and prevention.

There will always be some people who respond and others who do not. Having more options will allow doctors to personalize therapies for people living with RRMS.

With over a dozen available treatment options, why do we need more for RRMS?

There will always be some people who respond to specific treatments and others who do not. Having more options will allow doctors to personalize therapies for people with RRMS. Another reason is that our best treatments today only inhibit relapses by about 50 percent. We can do better than that! And more targeted immunotherapies could help stop the progression of RRMS without leaving a person with MS vulnerable to infections.

How important is a person with MS’s role in RRMS research and clinical trials?

The only way we can make progress in MS is by studying people with the disease. Patient-centered research efforts are gaining momentum. One of those efforts is the iConquerMS program, which is collecting data from 20,000 people about their lives with MS and their treatment responses. This will help answer questions about how environmental and lifestyle factors influence MS. People with MS can also take part in clinical trials of new MS therapies. They can find out about these at the National MS Society website.

The vision of National MS Society-funded research is to move us closer to a “World Free of MS.” While we are still searching for a cure, what does freedom from MS mean for people with the disease in real-life terms?

Freedom means something different to every individual living with MS. To some it simply means having the energy to enjoy dinner with their family at the end of the day. For others, it means being able to enjoy activities such as hiking, biking or painting.

CAROLYNN KIEL’S PANCREATIC CANCER WAS DETECTED EARLY BECAUSE SHE WAS AWARE OF HER FAMILY’S HISTORY WITH THE DISEASE AND HAD ANNUAL SCREENINGS.

CAROLYNN KIEL’S PANCREATIC CANCER WAS DETECTED EARLY BECAUSE SHE WAS AWARE OF HER FAMILY’S HISTORY WITH THE DISEASE AND HAD ANNUAL SCREENINGS.

After Carolynn Kiel lost her mother and sister to pancreatic cancer within the same year, her doctor recommended she get screened annually for an early detection marker for the disease. Even though she thought her physician was being overly cautious, she decided it was better to be safe than sorry. One year later, that screening resulted in an early diagnosis of pancreatic cancer that she believes helped save her life.

What many people don’t realize is that 10 percent of pancreatic cancer patients have a family history of the disease. In fact, the risk of developing pancreatic cancer more than doubles if a person’s mother, father or sibling had the cancer. Now, 13 years after her diagnosis, Carolynn wants to help raise awareness of how screening in high-risk individuals can help save lives, by sharing her family’s journey with pancreatic cancer.

When did pancreatic cancer first impact your family?

My sister Marilyn was diagnosed with pancreatic cancer in 2000. She was 58 years old, 11 months younger than me, and had flu-like symptoms that wouldn’t clear up. At the time, pancreatic cancer was a mystery to our family. The only person we knew who had pancreatic cancer was Michael Landon of Little House on the Prairie. Then my mother was diagnosed with pancreatic cancer about a year later after we noticed she was losing significant weight. My mom’s cancer was more advanced than my sister’s when she was diagnosed, so she lived only about two months after diagnosis. Then, just a few weeks later, my sister died as well.

Did that family history with pancreatic cancer change how you managed your health?

I thought our family was done with pancreatic cancer, but my primary care doctor said I should start getting tested annually for an early marker of pancreatic cancer called CA19-9. So I first got a blood test done looking for early signs in April 2003. That test came back negative. A year later, the CA19-9 marker came back positive, and a follow-up endoscopy led to my diagnosis of pancreatic cancer. I was mad. I said, “This isn’t fair!” I couldn’t believe that this disease affected the lives of so many people in one family.

CAROLYNN KIEL’S MOTHER (PICTURED ABOVE) WAS DIAGNOSED WITH PANCREATIC CANCER IN 2001 AND PASSED AWAY ABOUT TWO MONTHS LATER. HER DEATH SPURRED KIEL TO BEGIN ANNUAL PANCREATIC CANCER SCREENING, WHICH RESULTED IN AN EARLY DIAGNOSIS.

CAROLYNN KIEL’S MOTHER (PICTURED ABOVE) WAS DIAGNOSED WITH PANCREATIC CANCER IN 2001 AND PASSED AWAY ABOUT TWO MONTHS LATER. HER DEATH SPURRED CAROLYNN TO BEGIN ANNUAL PANCREATIC CANCER SCREENING, WHICH RESULTED IN AN EARLY DIAGNOSIS.

How did that early diagnosis affect your treatment?

We caught the disease early, so I was lucky to be a candidate for surgery. It is called the Whipple procedure. Only 20 percent of patients are eligible for the surgery. I was “lucky,” but that doesn’t mean the treatment was easy. The Whipple procedure is like going to hell, but you get to come back. It’s brutal. Getting through it requires a positive attitude and determination. I needed people to talk to, people who were going through the same thing as I was, and I found a pancreatic cancer support group. It made a significant difference in my life. So now, 13 years later, having survived my battle with pancreatic cancer, I make the time to talk with any pancreatic cancer patient who needs someone.

Do your other family members get screened for pancreatic cancer annually?

I worry about my daughter and sister. They’re tested once a year with the CA19-9 blood test and get annual checkups. With any cancer, early detection is the most important thing. Pancreatic cancer is so sneaky that by the time you have the symptoms, you’re already far along. The CA19-9 test isn’t something that’s included with regular blood work, so it’s important to check for it if you have a family history of pancreatic cancer. The CA19-9 marker is not perfect, but it is elevated in most people with pancreatic cancer. It’s one of the best things that we have right now for early detection.

CAROLYNN KIEL (FAR LEFT) AND HER FAMILY HAVE BEEN IMPACTED BY PANCREATIC CANCER. HER SISTER MARILYNN (LEFT) AND HER MOTHER (RIGHT) BOTH PASSED AWAY FROM THE DISEASE IN 2002. HER DAUGHTER STACY (FAR RIGHT) GETS ANNUAL SCREENING FOR THE DISEASE.

CAROLYNN KIEL (FAR LEFT) AND HER FAMILY HAVE BEEN IMPACTED BY PANCREATIC CANCER. HER SISTER MARILYNN (LEFT) AND HER MOTHER (RIGHT) BOTH PASSED AWAY FROM THE DISEASE IN 2002. HER DAUGHTER STACY (FAR RIGHT) GETS ANNUAL SCREENING FOR THE DISEASE.

There are ongoing studies and registries for individuals with a family history of pancreatic cancer to understand the genetic components of this disease better. Have you participated in any of these?

My daughter, sister and I had blood work sent to the National Familial Pancreatic Tumor Registry at Johns Hopkins probably 12 years ago. The information and blood work will help researchers determine the genetic and non-genetic risks for pancreatic cancer. It may help improve early detection, so more people can have a better shot of surviving like I did. I want to do anything that helps others. My attitude is that if there’s a slight chance it will help, then I will do it. What would stop anyone from helping out if they could?

What advice do you give people who are newly diagnosed with pancreatic cancer?

I tell people who are newly diagnosed to get a second opinion about their proposed treatments and even about their diagnosis. I also pass along advice given to me by my surgeon, which is not to go to a neighborhood hospital or a general surgeon for a Whipple procedure. Go to a surgeon who specializes in Whipple procedures. I also tell those same people to make sure their children and siblings get annual screenings. Early detection helps a lot with this disease.

To learn more about how patients cope with pancreatic cancer, read “Facing Each Day with Pancreatic Cancer, Hand-in-Hand.”

While progress made in immunotherapy is bringing hope to many patients, chemotherapy remains the backbone of treatment for the majority of patients living with non-small cell lung cancer. In some ways, researchers continue to evaluate the full potential of this foundational therapeutic class.

UPAL BASU ROY, DIRECTOR OF RESEARCH AND POLICY AT THE LUNGEVITY FOUNDATION EXPLAINS THAT CHEMOTHERAPY AND IMMUNOTHERAPY MAY MAKE A POWERFUL COMBINATION IN THE FUTURE.

UPAL BASU ROY, DIRECTOR OF RESEARCH AND POLICY AT THE LUNGEVITY FOUNDATION EXPLAINS THAT CHEMOTHERAPY AND IMMUNOTHERAPY MAY MAKE A POWERFUL COMBINATION IN THE FUTURE.

“We’re still learning how best to use chemotherapy and personalize it to help lung cancer patients live longer, better lives,” Upal Basu Roy, director of research and policy at the LUNGevity Foundation, said. “The role of chemotherapy in lung cancer treatment is still evolving and improving every day. I don’t see it ever really going away anytime soon.”

Lung cancer remains one of the deadliest forms of cancer, with an approximate 18 percent five-year survival rate. While certain subtypes of non-small cell lung cancer can be treated with targeted therapies, the majority are still treated with chemotherapy.

Fortunately, the experience of chemotherapy today is considerably less challenging than it was decades ago.

“When my grandmother was treated with chemotherapy for cancer in the 1980s, she suffered just as much from the side effects as she did from the cancer,” Basu Roy said. “But when my uncle was treated in the 2000s, his doctors prescribed him anti-nausea medications to help minimize that side effect.” Other medicines used along with chemotherapy aim to battle fatigue and loss of appetite.

By making chemotherapy more tolerable, doctors have expanded its use to earlier stages, when the disease has not spread (“metastasized”) beyond the lungs, so surgeons can attempt to remove the tumor. Chemotherapy before surgery can help shrink the tumor, making it easier to be removed. Giving chemotherapy soon after surgery is meant to kill any cancer cells left behind and has increased the five-year survival rate for patients with non-small cell lung cancer by 5 percent. When the tumor cannot be removed surgically, a combination of chemotherapy and radiation, given at the same time, has helped patients live longer.

We’re figuring out not only which treatment approaches are most effective but also how to combine them and in which order

With immunotherapies, which work with your body’s immune cells to fight cancer, the potential for innovative combination treatments with chemotherapy is growing. These new therapies have significantly reduced, or in rare case even eliminated, the tumor burden of metastatic disease in patients. But they don’t work for everyone. For instance, PD1 inhibitors work for 20 to 30 percent of patients with non-small cell lung cancer, meaning the remainder needs other options. Some studies are combining immunotherapy with chemotherapy to determine whether more patients respond.

With a rapidly changing treatment landscape, community oncologists who treat many types of cancer may not be up to date on the latest advances specific to lung cancer. So patients should learn all they can, ask plenty of questions and seek out second opinions from lung cancer specialists.

To provide the lung cancer community with the information needed to ask the right questions and make the best treatment decisions with their doctors, Celgene has worked with Cancer Support Community and LUNGEVITY to publish an educational resource called “Treatments for Advanced and Metastatic Lung Cancer” as part of the Frankly Speaking About Cancer® series. This guide is designed to help patients feel empowered to take control of their cancer—and their lives – and provides a comprehensive overview of treatment options for metastatic lung cancer, as well as a tear-out discussion guide to help patients understand what questions to ask and the type of information they need to work with their doctor to decide the best treatment options.

“We’re figuring out not only which treatment approaches are most effective but also how to combine them and in which order,” Basu Roy said. “And as we continue to learn, we need to make sure this information gets to the front lines, to the community oncologists who see the majority of lung cancer patients.”

To learn more about the treatment options for metastatic lung cancer, read Treatments for Advanced and Metastatic Lung Cancer at the Cancer Support Community website.

Dr. William Sandborn, Professor of Medicine and Chief, Division of Gastroenterology and Director, University of California San Diego Inflammatory Bowel Disease Center, believes the use of two co-primary endpoints for Crohn’s disease trials is raising the bar for new treatment options.

Dr. William Sandborn, Professor of Medicine and Chief, Division of Gastroenterology and Director, University of California San Diego Inflammatory Bowel Disease Center, believes the use of two co-primary endpoints for Crohn’s disease trials is raising the bar for new treatment options.

The last two years have seen dramatic changes in how researchers determine the efficacy of new therapies for Crohn’s disease. We’re now seeing findings from the first clinical trials to measure a therapy’s effectiveness through a combination of objective measures of the disease and patients’ evaluations of their own results.

Dr. William Sandborn, Professor of Medicine and Chief, Division of Gastroenterology and Director, University of California San Diego Inflammatory Bowel Disease Center, explains how this combination approach for Crohn’s disease trials is raising the bar for new treatment options.

What are the unmet needs for the treatment of Crohn’s disease?

While current treatment options for Crohn’s disease have demonstrated efficacy, their use may be limited due to multiple factors, including initial lack of response, loss of response over time or safety concerns. For instance, steroids have safety risks which increase if they are used for long periods of time, and the commonly used anti-TNF therapies can become less effective over time and can have serious side effects.

How have the endpoints for Crohn’s clinical trials been changing, and why?

Previously, we relied on a tool that did not accurately reflect the underlying biology of disease. That measurement, called the Crohn’s Disease Activity Index (CDAI), provided a score based on diaries that patients kept regarding their abdominal pain, stool frequency and how they felt overall (well-being). But those symptoms do not reliably correlate with the inflammation and sores in a patient’s bowels called ulcers.

To determine if a treatment is reducing the inflammation and ulceration of the gastrointestinal tract, doctors perform a colonoscopy, a diagnostic procedure used to examine a person’s digestive tract with a camera. As the Food and Drug Administration has sought to improve clinical trials in Crohn’s disease over the past two years, the field has been moving toward looking at both patient reported outcomes (how the patient feels) and the biological improvement that we can see in the intestine, which we call endoscopic improvement.

The Evolution of Endpoints in Crohn's Disease

How does this combination of endpoints compare with those used for clinical trials in other diseases?

Clinicians have been incorporating the patient’s experience and an assessment of the physical aspects of other autoimmune diseases for years. In multiple sclerosis, they look at patients’ descriptions of how they feel and function along with MRI of the brain that measures damage to the brain and nervous system. In arthritis, patients’ reports are combined with a physician examining the patient for joint damage, and for psoriasis physicians examine the patient’s skin inflammation. Crohn’s disease is now catching up with these conditions.

What are some of the challenges of looking at endoscopic changes?

The approach is still evolving, but we’ve done a lot in the past two years. We developed ways to measure endoscopic improvements and are using them in clinical trials for the first time now. While it’s not a perfect tool just yet, we are refining it based on our experience. You need a lot of training to interpret the data from a colonoscopy because it’s somewhat difficult to measure damage with a two-dimensional image. So we’ve been improving that training, and we’re also improving the system by video recording the procedures and having Crohn’s disease experts independently score the severity of the Crohn’s disease.

Ten years from now, I think that we will look back and realize that this was a seminal moment where we began to expect treatments to address the root causes of the disease.

Do you expect endoscopic improvements come before or after patients start feeling better? Why is that?

In general, there is a lag between when the patient feels better and when the bowel begins to heal in response to treatment, so we are learning that we have to wait longer to see those improvements. The emerging data from trials that have used endoscopic improvements suggest somewhere between four to six months might be the right time to evaluate intestinal healing. This evidence is causing us to rethink how we design clinical trials for Crohn’s and how we interpret results.

Aside from endoscopic effects, what are some other factors that are important to consider when analyzing potential new therapies?

Physicians are always looking at a drug’s balance of safety and efficacy. An effective treatment with an acceptable balance of side effects would be considered a step in the right direction. And if two therapies are otherwise similar, most physicians and patients would consider therapies that are taken by mouth, like a pill or tablet, over those given intravenously or through an injection.

Are you optimistic about future treatment options for patients with Crohn’s disease?

The evolution of clinical trial endpoints has been very exciting and is already having a significant impact on our search for new therapies. Ten years from now, I think that we will look back and realize that this was a seminal moment where we began to expect treatments to address the root causes of the disease.

As a modern class of therapeutics, antibodies continue to change the treatment landscape for cancer. Antibodies are naturally produced Y-shaped proteins whose “arms” grab hold of bacteria, viruses and other possibly dangerous cells while the “leg” recruits immune cells to destroy the invaders. Researchers have leveraged this ability of antibodies into a treatment approach called immunotherapy, in which antibodies, or pieces of antibodies, are designed in the lab to better recognize cancer cells as invaders and call in the immune system to kill them.

Immunotherapy has proven successful, with many drugs approved over the past decade. Now researchers are trying to improve on that success by splicing together portions of two antibodies with distinct targets to create what’s known as a bispecific antibody. The hope is that two targets will be better than one.

Bispecific antibodies may work two ways: either by blocking two pathways cancer cells use to thrive or by blocking one cancer pathway and simultaneously recruiting immune cells called T cells to tumors.

Bispecific Antibodies: Redirecting Immune Cells to Fight Myeloma

The concept of bispecific antibodies isn’t new (the idea has been kicked around since the 1970s), but interest has been renewed as the techniques to produce large quantities of these proteins have improved substantially over the past decade.

As a result, researchers are now able to explore their potential to combat many different cancers. In fact, the U.S. Food and Drug Administration has already approved two bispecific antibodies, and more than 30 others are being tested in clinical trials.

One cancer being tested is multiple myeloma, a disease that affects blood cells. Although researchers have made significant progress in the treatment of myeloma over the past decade, most patients will eventually relapse, meaning new therapies are in demand.

CAR-T cells and bispecific antibodies as single agents may offer new hope to patients with myeloma, but they also may provide the opportunity for new combinations with other novel targeted therapies under investigation.

Myeloma cells display a promising target for immunotherapy called B-cell maturation antigen (BCMA), which is found in 60 to 70 percent of multiple myeloma patients. So a new potentially successful bispecific antibody therapy might, for example, have one arm that binds to myeloma cells via BCMA and another that binds to T cells, one of the immune system’s top cancer assassins. While typical antibodies that bind to just one target also recruit immune cells, they generally do not specifically bring in T cells. A bispecific antibody with this ability is expected to have greater cancer-killing effects than conventional antibodies.

BCMA is also used in another immunotherapy approach for myeloma called chimeric antigen receptor T cells (CAR-T) therapy. In this strategy, a patient’s T cells are extracted, engineered in the lab to recognize and bind to BCMA, and then placed back into the patient. The goal is for CAR-T cells to home in on and destroy myeloma cells.

CAR-T cells and bispecific antibodies as single agents may offer new hope to patients with myeloma, but they also may provide the opportunity for new combinations with other novel targeted therapies under investigation. Ultimately, the aim with both tactics, alone or in combination, is to cure myeloma, a goal that seems more and more possible with every scientific advance.

To learn more about how immunotherapy is changing how we treat blood cancers such as myeloma, read “Immunotherapy May Be the Future of Myeloma Treatment.”

 

Discovering a new therapy is no easy task, and Esther Martinborough, executive director of research at Celgene, knows this firsthand. In 2008, she saw Receptos’ two therapeutic candidates for cancer fail before her team rallied to identify a potential new treatment option for multiple sclerosis (MS). Aided by the 2015 acquisition of Receptos by Celgene, her team is committed to bringing this potential new treatment option to MS patients.

In this Q&A, Martinborough explains that the company’s quick turnaround was due to two factors: the right team and a smarter way to screen therapeutic candidates.

Our Commitment to Multiple Sclerosis

ESTHER MARTINBOROUGH (FAR LEFT) EXECUTIVE DIRECTOR OF RESEARCH AT CELGENE< AND HER COLLEAGUES REVIEW DATA REGARDING THE COMPANY’S THERAPEUTIC CANDIDATE FOR MS.

What was Receptos’ original focus?

When the company was founded in 2008, we were called Apoptos and were focused on several exciting opportunities to develop anticancer therapies. After six months of preclinical research, it became apparent that we could not move forward. The scientific rationale was not holding together, and we explained this to our investors. Fortunately, our investors recognized we had a very qualified team with multiple individuals who had brought treatments to the market successfully. Based on that expertise, our investors put their trust in us and gave us another chance, so we worked as a team to carefully make sure our next hypotheses had the best chances of getting to the clinic. We were thorough, looking closely at multiple compounds and how they worked. We looked at a wide variety of candidates that were scientifically interesting.

Why did you choose to focus on a sphingosine-1-phosphate (S1P) modulator for MS?

There was a good biological rationale. Other S1P modulators were already in the clinic for MS, so we knew it could work. While the S1P compounds we evaluated weren’t quite ready for the clinic, we saw an opportunity to get them there quickly.

The S1P modulators that were ahead of us in clinical development, for the most part, had similar structures. We decided not to go down that same path.

How long has the development process taken?

We started working on our S1P modulator in March 2009 and were in the clinic less than two years later, which is quite simply astounding. When we began developing S1P modulators, about 20 other companies were ahead of us. Today, we’re one of the leaders in the pack.

How did you accelerate the development?

The difference was our screening approach. Most companies move step-by-step in screening candidates: they test the efficacy and then move onto studying the side effects and toxicology. We consolidated these steps into just one experiment. Using a biomarker for S1P as a preclinical measure of efficacy and lung weight in an animal model to measure safety, we were able to pick the therapeutic candidates with the right potential balance of efficacy and safety quickly.

ESTHER MARTINBOROUGH (RIGHT) AND A COLLEAGUE AT CELGENE DISCUSS THE CHEMICAL STRUCTURE OF THE COMPANY’S S1P MODULATOR THAT IS CURRENTLY IN CLINICAL DEVELOPMENT FOR MS.

ESTHER MARTINBOROUGH (RIGHT) AND A COLLEAGUE AT CELGENE DISCUSS THE CHEMICAL STRUCTURE OF THE COMPANY’S S1P MODULATOR THAT IS CURRENTLY IN CLINICAL DEVELOPMENT FOR MS.

What made this S1P modulator stand out from the others being developed?

The S1P modulators that were ahead of us in clinical development, for the most part, had similar structures. We decided not to go down that same path because that would likely only lead to the same safety and efficacy profiles. Instead, we designed chemical structures in our S1P modulator that were different from those already reported. We looked to map out a unique chemical space that could benefit MS patients.

Learn more about the role of S1P signaling molecules in MS and other immune-inflammatory diseases, read “Corralling White Blood Cells to Rein in Multiple Sclerosis.”

When recruiting patients for a clinical trial, it is important that researchers select the right mixture of people—in terms of age, gender and ethnicity—who they’re seeking to treat with a new therapy or treatment intervention. This variety is critical for researchers to understand how treatments impact patients differently. Unfortunately, achieving diversity in clinical trials continues to be a challenge.

While African Americans make up over 20 percent of newly diagnosed multiple myeloma cases in the United States, they represent only 8 percent of cancer clinical trial participants. When it comes to multiple myeloma, a cancer of a type of white blood cells called plasma cells, African Americans are twice as likely to be diagnosed with the disease, which makes it even more important that they are better represented in myeloma clinical trials.

Meanwhile, African Americans are more likely than any other racial group to be diagnosed with and die from cancer. African Americans have also benefited less from advances in myeloma treatment over the past two decades than whites, suggesting unequal access to or response to treatments.

African Americans & Myeloma Clinical Research

“Without a doubt, African Americans are underrepresented in myeloma trials,” Brendan Weiss, an assistant professor of medicine at the University of Pennsylvania who specializes in myeloma, said. “Now that new tools like next-generation DNA sequencing can shed some light on the genetic diversity in myeloma, studies should absolutely do the best they can to try to get diverse representation.”

Understanding the genetic differences between African American patients and other patients with myeloma could go a long way in explaining the differences among different patient groups in how the disease progresses and responds to treatment. As a result, doctors may get more insight into how to treat the disease most effectively for each group.

Alfiee Breland-Noble, an associate professor of psychiatry at Georgetown University, explains why minorities have a mistrust of the American medical system.

Alfiee Breland-Noble, an associate professor of psychiatry at Georgetown University, explains why minorities have a mistrust of the American medical system.

But recruiting African Americans for trials has been difficult. In one 2013 survey, African Americans were more likely than any other racial group to cite lack of trust as a reason not to participate in a clinical trial and to believe that patients are sometimes enrolled in trials without their consent.

“African Americans have a historical mistrust of the medical system,” said Alfiee Breland-Noble, an associate professor of psychiatry at Georgetown University who studies disparities in clinical trials. “A lot of that mistrust comes from people feeling like they’re not treated equally in the health care system.”

To boost enrollment of African Americans in clinical trials, including those of myeloma therapies, clinicians have to build an environment of trust. Clinics must be proactive in communicating the value of clinical trials consistently—with pamphlets in the waiting room, for example, not just when recruiting patients—so people can begin to learn why participation is so vital to improving the understanding of disease and treatments for everyone.

The message we want clinicians to get across to African American patients is: you are needed, you are important, and we need to know how these medications impact people like you.

For instance, one study found that providing patient navigators to help guide patients and answer their questions about the process raised the enrollment rate of eligible African American cancer patients to about 80 percent. Another group found that African Americans who participated in a clinical trials education program through their local church were almost three times as likely to enroll in a clinical trials registry.

“The message we want clinicians to get across to patients is: you are needed, you are important, and we need to know how these medications impact people like you so that we can help other people like you,” said Breland-Noble.

Diversity among researchers, clinicians and clinic staff can also help patients of various backgrounds feel more comfortable throughout their care. It’s a sentiment that Celgene’s Standing in the Gaap initiative is already embracing, with efforts to boost the numbers of students pursuing cancer research and medicine at historically black colleges and universities.

By making the field of myeloma care and research more diverse, the campaign aims to make African American patients feel more included and more likely to participate in clinical trials. It’s only then that researchers can study the full links between genetics and myeloma.

Discover more information about how myeloma affects African Americans on the Standing in the Gaap Facebook page.

At some point during their life, approximately 0.7 percent of men and women will be diagnosed with multiple myeloma, a cancer of white blood cells. A disproportionate number of these diagnoses occur in African Americans; while African Americans represent approximately 13 percent of the U.S. population, they make up about 20 percent of myeloma patients. Multiple myeloma is the second most common blood cancer in the United States, but the most common among African Americans.

“Multiple myeloma is often thought of as a disease impacting older individuals, particularly older white males,” Valerie Kobzej, the director of myeloma marketing at Celgene, said. “But if you look at the data, African Americans are twice as likely to be diagnosed with the disease.”

To put it another way, take a million white Americans, and 75 men and 45 women will be diagnosed with myeloma. For African Americans, those numbers more than double to 151 men and 112 women. Moreover, African Americans are afflicted at a younger age — on average, they’re about five years younger than whites at diagnosis.

Myeloma Twice As Likely To Strike African Americans

Scientists don’t completely understand the reason for the racial discrepancy yet, but they have some ideas. People with the blood disorder called monoclonal gammopathy of unknown significance (MGUS) have a higher risk for developing myeloma, and African Americans are more than twice as likely than other races to develop MGUS.  Another study found that more than one-third of African-Americans with these diseases carry the protein pP-7, an inherited risk factor for MGUS and myeloma.

We believe it’s really important that African American patients already diagnosed with myeloma know there is hope.

The positive news for African Americans with myeloma is they can do just as well as, if not better than, white Americans when they receive a timely diagnosis and proper treatment. And African Americans may have a biological tendency toward less aggressive forms of the disease. Unfortunately, African Americans are also more than 40 percent less likely to receive the type of care that white Americans receive.

African Americans have also had smaller improvements in survival over the past 40 years than have white Americans. This disparity in survival may be due to problems accessing the best therapies.

The myeloma burden and treatment gap among African Americans highlight the critical need for raising awareness and working toward equal access for treatments. It’s this sentiment that inspired Celgene to launch their Standing in the Gaap initiative.

“We believe it’s really important that African American patients already diagnosed with myeloma know there is hope,” Kobzej said.

Celgene launched the Standing in the Gaap initiative to bridge the gaps in care for African Americans with multiple myeloma.

Celgene launched the Standing in the Gaap initiative to bridge the gaps in care for African Americans with multiple myeloma.

Through the initiative, which includes a Facebook page and other online resources, Celgene hopes to work with historically black colleges and universities as well as the U.S. Congressional Black Caucus to bring multiple myeloma to the forefront of research and care. The campaign aims to educate people about how myeloma affects African Americans, improve the quality of their care and ultimately improve survival rates.

Learn more about the Standing the Gaap initiative on Facebook.

 

According to a National Psoriasis Foundation survey, 25 percent of people living with moderate psoriasis are not receiving treatment, and 30 percent are being undertreated with only topical medications. These patients face an uphill battle in getting a proper diagnosis and accessing treatment options that could improve their lives.

VIEW THE COMPLETE “How Severe Is My Psoriasis?” INFOGRAPHIC

VIEW THE COMPLETE “How Severe Is My Psoriasis?” INFOGRAPHIC

Psoriasis is an inflammatory disease that causes red, scaly patches on the skin, most commonly on the elbows, knees or scalp. Dermatologists classify a patient’s disease as mild, moderate or severe based on how much of the body is affected. If less than 3 percent of a patient’s body is covered with psoriasis, it is considered mild, and if more than 10 percent is affected, it is considered severe. Those cases that fall in between are called moderate.

“Unfortunately, it’s an imperfect diagnostic tool that fails us often,” said Dr. Abby Van Voorhees, the chair of dermatology at the Eastern Virginia Medical School and chair of the National Psoriasis Foundation medical board. “It doesn’t take into account the impact of the location or the severity of inflammation on a patient’s life.”

For instance, a patient with psoriasis on the palm of his or her hands would technically have a mild case based on the small area affected, but the location could be debilitating. That impact on the patient’s life might justify classifying this case as more severe, according to Van Voorhees.

Traditionally, dermatologists have prescribed topical medications for mild psoriasis and systemic therapies for those with severe psoriasis. But for the 40 percent of psoriasis patients who identify their disease as moderate, few treatments really addressed their unique needs. As a result, doctors had little choice but to prescribe topical treatments for most moderate psoriasis patients.

To improve the lives of patients stuck in between mild and severe psoriasis, we need to educate doctors and insurers about the impact of moderate psoriasis on patients’ lives and about the potential of these new treatments.

However, new treatment options for moderate psoriasis have recently become available and are continuing to be explored. “New data is continuing to come out that shows these new therapies can improve patients’ lives and lower their risk for other diseases with minimal risk,” Van Voorhees said. “Dermatologists need to stay informed and encourage patients to explore these treatment options for moderate psoriasis.”

Even if a dermatologist prescribes a new therapy, insurance companies could still deny coverage. Insurers often only cover systemic therapies if 10 percent or more of a patient’s body is affected by psoriasis, meaning only severe psoriasis patients would have access to these therapies. According to a 2014 study, insurance problems were one of the top reasons psoriasis patients stopped taking their treatment.

“It’s very distressing but not surprising,” Van Voorhees said. “To improve the lives of patients stuck in between mild and severe psoriasis, we need to educate doctors and insurers about the impact of moderate psoriasis on patients’ lives and about the potential of these new treatments.”

When patients are diagnosed with pancreatic cancer, doctors often tell them there are limited treatment options and to prepare for the worst. For pancreatic cancer patient and advocate Anne Glauber, though, a patient-first approach to treatment is helping her beat the odds. Glauber explains why patients need to make their voices heard during treatment.

When did you learn that you had pancreatic cancer? How has it affected your life?

I was diagnosed with stage IV pancreatic cancer in May 2014, and, to put it mildly, it has completely transformed my life. I had no signs or symptoms at all until a week before my diagnosis when I got jaundice and was feeling tired. I thought it was just because of my busy schedule; I was working as a managing partner at the public relations firm Finn Partners, co-founded NO MORE, had just published a book and was busy with pro bono projects as well. My diagnosis was shocking and devastating. My entire life halted.

How important was it to know that you were not alone at that time?

I couldn’t have gotten through that shock without the support of my family, my children Lili and David, my partner Dave and my close friends   They all helped me research where I should go for treatment and who the best pancreatic cancer specialists in the country were.

Anne Glauber was diagnosed with stage IV pancreatic cancer in 2014 and since then has advocated for a patient-first approach to pancreatic cancer treatment. Source: Anne Glauber

Anne Glauber was diagnosed with stage IV pancreatic cancer in 2014 and since then has advocated for a patient-first approach to pancreatic cancer treatment. Source: Anne Glauber

How limited were your treatment options?

When I was diagnosed, the doctor told me there were two treatment options—both had side effects but could possibly give me a couple of extra months to live. I went to the top cancer institutes in the country and heard the same things—they were offering me standard-of-care treatments. A friend recommended that I meet a doctor in Los Angeles, so my family and I packed our bags. Our planned three-day trip turned into a month-long stay after speaking with him about his treatment approach. He is creative and innovative in treating pancreatic cancer. I was introduced to another doctor at New York Presbyterian, who is now handling my day-to-day care and is also very innovative and shapes treatments that are personalized to my tumor. They introduced me to scientists involved with cutting-edge research.

How has that research informed your treatment?

It’s made it more personalized. We’ve incorporated approaches to make the cancer more susceptible to treatment, including investigative research in circulating tumor cell analysis. I also have an organoid, which are my tumor cells living in a lab dish. These cells can be tested with thousands of different possible treatments to see what can be effective for my pancreatic cancer. My organoid was created by scientists led by a researcher at the Lustgarten Foundation’s Pancreatic Cancer Research Lab at Cold Spring Harbor Laboratories.

Why is it important for patients to make sure their voices are heard?  

I think pancreatic cancer patients need to be informed about their treatment and to advocate for science-driven care that can be personalized to their unique tumor and cancer. Patients and families need to be educated about science-driven options beyond the standard of care so they can ensure that they are getting the best treatment possible for them.

We need to make sure insurance keeps pace with the science. Personalizing treatment is really, really critical for pancreatic cancer patients.

Because I’ve personally seen what the science can do, I became a board member of the Lustgarten Foundation, the largest private funder of pancreatic cancer research. I am also working on launching an interactive website called “Let’s Win” that will help pancreatic cancer patients share information about treatment with each other and learn about new a science advances and clinical trials. Let’s Win will be launched in May.

What should we as a society be focusing on with regard to pancreatic cancer?

There’s no cure for pancreatic cancer, and I don’t know if we’re anywhere close to a cure. We need to get more resources to explore personalized medicine further. We need to make genomic analysis easier to access and have better insurance coverage for it. While some things like organoids and circulating tumor cell analysis remain investigational, we need to make sure insurance keeps pace with the science. Personalizing treatment is really, really critical for pancreatic cancer patients.

What would you like people to know about pancreatic cancer on Rare Disease Day?

We need more resources dedicated to pancreatic cancer research. We need to get more funding for scientists who are making great strides in detecting and treating this disease. Pancreatic cancer is underfunded, especially given the relatively high mortality rates. We must have more funding for research into this disease.

While improvements in the treatment of multiple sclerosis (MS) have focused on reducing the frequency of flare-ups, preventing MS-related disability has remained a struggle. Multiple sclerosis and other immune-inflammatory diseases can flare up when white blood cells go rogue—exerting their inflammatory effects where they shouldn’t. Scientists have recently identified methods to corral these rogue cells, lessening their ability to inflict damage, by blinding them to the signposts that lead them astray. The latest research now aims to refine this method, to lessen potentially dangerous side effects.

Unwanted, uncontrolled inflammation can wreak havoc in the body. It’s at the root of multiple sclerosis and countless other disorders, including Crohn’s disease and ulcerative colitis. Research has shown that the damage can be partly blamed on an invasion of white blood cells called lymphocytes. As a result, several strategies have been devised to interfere with their migration to inflammation sites.

In one such strategy, lymphocytes are made “blind” to the signals that lead them out of hiding and send them off in search of inflammation. When they aren’t off finding enemies to fight, lymphocytes can often be found hanging out in lymph nodes, where they are relatively harmless. But they can be lured out of nodes by a signaling molecule called sphingosine 1‐phosphate (S1P). Nodes have little S1P, while the blood vessels they sit near have much more S1P, and the white blood cells follow the trail of S1P to escape their hiding spots.

Lymphocytes can be lured out of nodes by a signaling molecule called sphingosine 1‐phosphate (S1P).

Once in the bloodstream, lymphocytes are free to wander to places where they might do damage—like an inflamed intestine, in the case of Crohn’s disease, or a vulnerable neuron, in the case of multiple sclerosis. But their escape from lymph nodes can be blocked by modulating the receptors that sense S1P, known as the sphingosine 1‐phosphate receptor (S1PR) family.

Therapies that interfere with S1PR aim to trap lymphocytes in lymph nodes, reducing their numbers in the bloodstream and tissues. And at least one such therapy has been successful in treating certain forms of multiple sclerosis.

Interfering with the S1PR family can have its drawbacks, though. For instance, since one S1PR member is involved in cardiac function, patients have to be monitored for several hours after their first dose, to ensure their heart continues to work properly. As a result, researchers are looking for therapies that more specifically target only the S1PR members that let lymphocytes out of nodes. The aim is to improve the reduction in inflammation while also reducing the chances of potentially dangerous side effects.

G-protein-coupled receptors

Members of the S1PR family belong to a class of membrane receptors known as G-protein-coupled receptors (GPCR). These proteins are like signal transducers—taking messages from the environment in the form of sugars, fats, protein and even light and translating them into changes inside cells.

Humans have almost 1,000 different GPCRs, and each recognizes and responds to a particular signal. They have so many different functions that it’s thought between a third and a half of all marketed drugs act by binding to GPCRs.

GPCRs have a very distinctive shape and structure: a protein chain that wraps back and forth seven times from the outside of the cell to the inside and back. The loops facing out of the cell form a landing site for signaling molecules. Inside the cell, GPCRs interact with the partners that give the receptors their name: G proteins.

G proteins are like on-off switches that can be flipped depending on the state of its GPCR. G proteins have three parts: α, β and γ. When the three are bound together with their GPCR, α binds a compound called guanosine diphosphate (GDP), which keeps it in an “off” state.

When the right signal outside the cell—a sugar, for example—binds to the GPCR, the receptor changes shape, kicking α and its GDP out of the group. The change also causes GDP to be replaced with guanosine triphosphate (GTP), which creates an “on” state. It’s this active α subunit that travels through the cell turning on specific cellular activities.

Back at the cell membrane, the now lonely β and γ portions of the G protein also relay messages into the cell. For instance, they can activate (or inhibit) enzymes or open up (or close) ion channels. The resulting metabolic changes allow the cell to respond to an ever-evolving environment.