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Multiple Myeloma: A Rare and Complex Cancer

We continue our series on multiple myeloma with an interview with Gareth J. Morgan, MD, FRCP, FRCPath, PhD, professor of hematology and director of the Myeloma Institute at the University of Arkansas for Medical Sciences (UAMS). Dr. Morgan also serves as deputy director of the Winthrop P. Rockefeller Cancer Institute at UAMS.

Dr. Morgan is responsible for all clinical, research, and administrative operations at the Myeloma Institute, which is one of the largest programs in the world focused on the research and treatment of multiple myeloma and related diseases. Clinically, he directly oversees 8 physician specialists, 14 mid-level providers, and 7 hospitalists, all experts in the management of myeloma and related plasma cell diseases. He also manages 8 research teams, which represent an integrated program of the genetics and biology of myeloma.

Mechanisms of Malignant Transformation

Real World Health Care: What got you interested in the field of multiple myeloma and what keeps you inspired?

Dr. Gareth Morgan, University of Arkansas for Medical Sciences

Gareth Morgan: Scientifically, I saw the opportunity to exploit the transition of MGUS (monoclonal gammopathy of undetermined significance) to smoldering myeloma to multiple myeloma as a model to understand the mechanism that drives malignant transformation. I reasoned that if we understood these, we should be able to manipulate them therapeutically.

I continue to be inspired by the ability to translate the biology and genetics of myeloma into clinical practice, where better and less toxic treatments can and are being developed to help patients achieve better outcomes and increased survival. Patients are the true source of inspiration.

Myeloma Genome Project

RWHC: Tell us about your recent research work and its significance to the multiple myeloma patient community.

GM: This is an exciting time for the field of myeloma, and our research investigations have led to some exciting discoveries in the biology of myeloma based on the genetic variations within the human genome. With our colleagues in Europe, have identified eight new genetic variations that could be linked to an increased risk of developing myeloma.

We are also focused on developing a molecular classification of myeloma based on patient subgroups with distinct pathogenesis and clinical behavior. We have partnered with Celgene and the Dana–Farber Cancer Institute in establishing a global collaboration called the Myeloma Genome Project. The goal of this project is to compile and analyze the largest set of genomic and clinical data to design a molecular classification system to improve the diagnosis, prognosis and treatment of myeloma. Up to this point, we have collated the data that we already have, and now we are bringing other national and international investigators in to really form a global consortium. This data will help us identify patients who have distinct clinical outcomes, and allow us to take a stratified-risk approach to designing treatment strategies. This initiative could really lead the way in developing specific clinical trials for targeted treatments for patients in the future.

Personalized Medicine: The Future of Cancer Care

RWHC: What are the most promising new treatments for multiple myeloma? Are there any on the horizon that hold the possibility for a cure?

GM: I believe that stem cell transplantation remains the backbone of treatment for many patients, and we don’t want to move away from a strategy we know to be successful for many. So, we are now incorporating new treatments to increase cure rates and to give more patients higher and better responses overall. This involves moving away from the one-size-fits-all approach to a more directed, personalized one which includes the use of novel agents, immunotherapy, and targeted-based treatments.

Immunotherapy is one of the more exciting developments for patients with relapsed/refractory disease, and we are now looking at incorporating these agents into the newly diagnosed setting. Using different combinations of antibodies that address the different components of the immune system is going to be a really important way forward. In addition, the increased understanding of cancer genomics has given us a wealth of information about the biological processes involved in the initiation and development of myeloma cells, which has really powered the concept of developing targeted therapies directed at specific mutations at the molecular level. This approach, also known as personalized or precision medicine, clearly represents the future of cancer care.

Underlying Causes of Myeloma

RWHC: What are some of the biggest challenges facing multiple myeloma researchers?

GM: Some challenges myeloma researchers face include gaining a better understanding of the underlying causes of myeloma and designing prevention and early intervention strategies, as well as developing strategies to prevent precursor states of myeloma—MGUS (monoclonal gammopathy of undetermined significance) and smoldering myeloma—from developing into active multiple myeloma. Of course, funding remains one of the biggest challenges faced by researchers, and it probably always will be.

Increasing collaborations with university and industry partners provides an opportunity to gain access to much larger datasets and to develop clinical trials to help answer some of these important questions.

Overcoming Resistance to Multiple Myeloma Treatment

RWHC: What are some of the biggest challenges facing clinicians treating multiple myeloma patients?

GM: Over the last decade, we’ve seen an unprecedented improvement in multiple myeloma as novel agents and treatment combinations expand. Despite the vast improvement, there remains a proportion of patients who relapse and are more likely to have aggressive disease that is refractory to therapy. I think one of the challenges in myeloma is how do we treat and design strategies that can overcome treatment resistance for these high-risk patients to improve their long-term outcomes.

This challenge requires a change that focuses on the use of genetic analyses to segment myeloma at the molecular level to enhance risk segmentation to develop biologically-stratified treatment approaches. We are also exploring the use of imaging studies to recognize high-risk and DNA-based features. Collecting the sequencing and imaging data and analyzing it consistently provides a resource for the myeloma community that can continue to grow into the future.

Another important challenge facing clinicians is patient access to a myeloma specialist. Myeloma is a rare and complex cancer, so oncologists can’t use concepts developed for more common cancers, such as breast or colon, in myeloma. The key is having a focused strategy that is directed by a myeloma expert. Unfortunately, some patients don’t have access to a specialist because of location, insurance, or other financial restrictions. At the Myeloma Institute we incorporate a team approach, whereby our team of myeloma experts direct the treatment strategy and for practical purposes, patients can receive much of their treatment locally. So, if myeloma experts can partner with local oncologists who can then deliver some of the treatment, then it’s an ideal setting for patients, because they receive the benefit of a myeloma-specific strategy and risk stratification upfront, and in the long-term, they have the comfort and security of being close to home.

 

Juvenile Arthritis Awareness Month Underscores Efforts to Identify Causes and Develop Treatments

That’s right. Children get arthritis too. In fact, according to the Arthritis National Research Foundation (ANRF), nearly 300,000 children in the U.S. have been diagnosed with juvenile arthritis (JA) – one of the most common childhood diseases in the country.

Linda Barlow

Linda Barlow 

When Juvenile Rheumatoid Arthritis (JRA) first shows its symptoms in a child’s body, many parents write off swollen joints and fever as the flu, or think a sudden rash might have occurred from an allergic reaction. The symptoms might even recede slightly before showing up again, sometimes delaying diagnosis. 

Because a child’s immune system is not fully formed until about age 18, JRA can be especially virulent, compromising the body’s ability to fight normal diseases and leaving children open to complications that can adversely affect their eyes, bone growth and more.

Both the Arthritis Foundation and the ANRF are on the forefront of combatting this disease by supporting research into causes and treatments.

The ANRF’s Kelly Award is one example of how the organization dedicates part of its research effort toward treatment of JRA. The $75,000 grant is given annually to a researcher focused solely on JRA treatment and cures. For the past two years, the award went to Dr. Altan Ercan at Brigham & Women’s Hospital in Boston, whose work has the potential to provide novel targets for new therapies.

Another example is the Arthritis Foundation’s partnership with the Childhood Arthritis and Rheumatology Research Alliance (CARRA). Through the partnership, the Foundation is working to create a network of pediatric rheumatologists and a registry of children with the disease, allowing researchers to identify and analyze differences and similarities between patients and their responses to treatment. Ultimately, the registry will help researchers cultivate personalized medicine, the ultimate weapon in battling the disease. The CARRA Registry has been launched at 60 clinical research sites and has enrolled 8,000 patients.

The Arthritis Foundation has also committed to providing more than $1.1 million in funding this year to researchers investigating a wide range of topics, including: 

  • Exploring how environmental and genomic factors might play a role in triggering juvenile arthritis; 
  • Collecting data and evaluating the efficacy of standardized treatment plans; and 
  • Developing and testing a smart phone app to help children cope with pain.

According to the Arthritis Foundation, there is no single test to diagnose JA. A diagnosis is based on a complete medical history and careful medical examination. Evaluation by a specialist and laboratory studies, including blood and urine tests, are often required. Imaging studies including X-rays or MRIs may also be needed to check for signs of joint or organ involvement.

“When joint pain, swelling or stiffness occurs in one or more of your child’s joints for at least six weeks, it’s important not to assume these symptoms are temporary, and to get a proper diagnosis from a pediatric arthritis specialist,” says Arthritis Foundation Vice President of Public Health Policy and Advocacy, Dr. Patience White. “Early medical treatment of juvenile arthritis can prevent serious, permanent damage to your child’s joints and enable her to live an active, full childhood.”  

Management of JA depends on the specific form of the disease but can include:

  • Care by a pediatric rheumatologist.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) to control pain and swelling.
  • Corticosteroids such as prednisone to relieve inflammation, taken either orally or injected into inflamed joints.
  • Biologic Response Modifiers (BRMs), such as anti-TNF drugs to inhibit proteins called cytokines, which promote an inflammatory response. These are injected under the skin or given as an infusion into the vein.
  • Disease-modifying anti-rheumatic drugs such as methotrexate, often used in conjunction with NSAIDs to treat joint inflammation and reduce the risk of bone and cartilage damage.

One promising therapy in the fight against juvenile arthritis has been recently approved by the Food and Drug Administration – Actemra (tocilizumab) – from Roche. Used to treat polyarticular juvenile idiopathic arthritis (PJIA), the medicine can be used in children ages 2 and older. It is also approved for the treatment of active systemic juvenile idiopathic arthritis (SJIA).

How can organizations like the Arthritis Foundation and the ANRF increase awareness that arthritis happens to children, and build support to advance development of research and therapies?