Hope through New Research into Myelodysplastic Syndromes

Research is leading to new, more personalized treatment options.

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?”