Research led by Dr. Gareth J. Morgan could result in prevention therapies that enable researchers and clinicians to intervene before multiple myeloma develops.
Photo: ºÙºÙÊÓƵ Staff
Gareth J. Morgan, MD, joined ºÙºÙÊÓƵ Health’s Perlmutter Cancer Center in February 2019 as director of multiple myeloma research. A professor in the , Dr. Morgan focuses his research on the genetics and biology of multiple myeloma, a blood cancer that affects plasma cells in the bone marrow that can cause anemia and weakened bones as well as infections and kidney problems.
Recent advances in multiple myeloma have improved outcomes for people with this chronic condition and transformed this area of medicine. In the next decade, research by Dr. Morgan and others could result in prevention therapies that enable researchers and clinicians to intervene before the cancer develops. Dr. Morgan is part of the leadership team of the new Center for Blood Cancers, a robust clinical research program that Perlmutter Cancer Center is building to help lead the way in both these areas.
He discusses advances in treatments, goals for improving outcomes for people with multiple myeloma, and more.
As director of multiple myeloma research, what are your goals for treating this disease?
I have been at Perlmutter Cancer Center for a year now and have spent that time setting up the research laboratory so that we can perform translational research on clinical samples. I recently received my New York State medical license and can now take advantage of the hard work we have invested to optimize myeloma patient care management.
From an aspirational point of view, we aim to be a global leader for management and research on multiple myeloma and its precancerous phases. This goal lies well within our grasp, and I am excited to be setting out on this important journey. A key strategy to achieve this will be to build links with providers across the ºÙºÙÊÓƵ healthcare system to facilitate a team-based approach to patient care management. We have superb clinical and molecular infrastructure, and we will use this to move from a concept where one size fits all to an approach to myeloma therapy that is more personalized and based on targeting specific therapy to an individual patient’s myeloma biology.
Our initial aim is to build on therapeutic advances in myeloma treatment that have occurred over the past decade. Ultimately, our goal is to cure patients with multiple myeloma. While several novel treatments have been approved by the U.S. Food and Drug Administration over the last 10 years, knowing how to optimize their use remains a clinical challenge. Our strategy to achieve cure is to segment patients into distinct therapeutic groups and target specific therapies to each group.
What is the current standard of care for people with multiple myeloma, and what are your goals for improving outcomes?
Dividing patients into groups where specific therapies are the most appropriate is a key to good oncology care.
Older patients or patients in less good health with multiple myeloma require specific approaches to optimize response rates while maximizing quality of life and avoiding therapeutic toxicity. The role of genetic approaches in determining therapy for these cases remains largely unknown, and we see it as a major opportunity to understand this relationship and expand the knowledge base. By contrast, more is known about the genetics of young, fit patients with myeloma where aggressive clinical care options, including high-dose chemotherapy and stem cell transplant, have become our standard. For older patients, less able to withstand the consequences of the high-dose chemotherapies, alternate approaches are required that can be equally effective but less toxic. This is becoming increasingly possible as our therapeutic toolkit expands.
Standard myeloma treatment approaches include induction therapy, stem cell transplant, consolidation, and maintenance. The drug combinations used in each of these steps can be designed to maximize responses and achieve minimal residual disease (MRD) states, where the disease only can be detected using sensitive diagnostic tests. Our hypothesis is that each of these steps should be optimized to increase the number of patients achieving MRD-negative states, which we have shown to be associated with prolonged survival and cure. This therapeutic strategy is now applicable across all age and performance status groups.
To complicate decision-making further, multiple myeloma is made up of at least six different molecular subtypes, each of which has a distinct biology and clinical outcome. If we are to maximize outcomes, I believe that each of these subtypes should be treated differently.
Another key subgroup where we can make a significant impact on survival is high-risk myeloma (defined as a median survival of only 12 to 18 months), where outcomes have remained poor and patients have not benefited from the use of novel therapies. We think that if we can shine the spotlight on these patients by conducting , we should both be able to understand the biology of their disease and systematically improve outcomes.
While treatment is important, prevention could drastically change our approaches to managing cancer in the next decade. Approximately 5 percent of patients over the age of 60 have precancerous forms of disease known as monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM). The disease entities transform to myeloma at a rate of 1 to 10 percent per year. We are studying the genetics of these disease stages to define ways to identify patients whose disease is at greater risk of transforming so that early intervention is possible to prevent cancer from developing.
How has treatment for multiple myeloma advanced, and what are some of the advances that are on the horizon for patients?
I have looked after people with myeloma for more than 25 years now, and in that time the outcome for patients has changed dramatically. At the start of my career, therapy options were limited to a handful of drugs, and few patients with myeloma survived for even three or four years. The novel therapies have dramatically improved patients’ quality of life and have substantially increased survival and reduced the impact of bone disease. However, it’s really only in the last few years that we have started to talk about the potential for cure for a subset of patients.
For the precancer stages (MGUS and SMM) an outstanding question is whether early treatment can increase cures and prevent the predicted increase in clinical cases as the population ages. To effectively address the value of early intervention, we will establish a prevention clinic at Perlmutter Cancer Center where patients with these conditions can be fully assessed and their risk of transformation identified. This clinic will allow us to focus our efforts on clinical and molecular investigation to determine the length of time the disease has been present, its evolutionary diversity, and its likelihood of transformation. In this way, we will determine whether early therapeutic intervention is necessary and whether it can truly impact outcome.
When you meet with people with multiple myeloma, what kinds of questions do they usually have?
One thing that patients always ask is what caused this disease. Although a few environmental risks are known, in the majority of patients the cause is not known. We’ve done a lot of work looking at the causes of myeloma at the genetic level. And while it’s not a genetic disease, we found a number of genes that can increase the risk of developing myeloma. We are pushing this project forward by looking at genetic signatures generated by the immune system to understand why African Americans have a two- to threefold excess incidence in comparison with European Americans. This is one of our major research focuses currently, and we hope to build intervention strategies, which could mitigate this excess incidence.
