MCRI Research Update: Creating an Immune System Signature for Myeloma Patients to Predict Response to Treatment with David Chung, MD, MSKCC
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The Myeloma Crowd Research Initiative (MCRI) taps into the power of crowdsourcing and crowdfunding to find and fund the best ideas, research and clinical applications leading to new myeloma treatments or potential cures. Currently, the MCRI is funding three research projects:
Dr. Chung, MD, PhD - Creating an Immune System Signature
Dr. Rodriguez, MD - Testing Your Individual Myeloma Tumor Against Available Myeloma Therapies
Dr. Zhan, PhD - Targeting CD24 to Eliminate Myeloma Stem Cells
We recently spoke with each research project to provide an update. Thank you to our incredible donors for helping make this research possible!
Here is an exciting update from Dr. Chung on Creating an Immune System Signature:
The myeloma research community is learning that the immune system plays a significant role in how well patients respond to therapy and maintain their responses. As many therapies are immune-based, we need to learn more about how the immune system works.
While all myeloma patients have some immune system weakness (or we would have never developed myeloma), some patients have stronger immune systems than others. Today there is no “standard” immune system panel that can be run in a lab that can tell myeloma patients if their immune system is worn out or is robust enough to maintain a good response after myeloma treatment.
Dr. Chung has received funding from the MCRI to do just that – identify key immune system markers with the goal of creating an immune system panel that will indicate the “health” of the immune system to help predict response to therapy.
In a pilot study published three years ago, Dr. Chung and his team used flow cytometry on patient samples following transplant to assess immune profiles and learned that in general, patients who relapse within 2 years of stem cell transplant had changes indicative of a more exhausted immune system than those who do not.
But which specific markers are important? The field of cancer immunology is advancing at a rapid pace, with some markers just being discovered in the last 5 or 10 years. Newer technology is now being used by Dr. Chung’s team to assess multiple combinations of immune markers (like CD markers found in flow cytometry or infection fighting T cells like CD4 and CD8) that may or may not be important. He has also incorporated newer testing platforms to maximize the use of the donated blood samples and leverage the samples that have already been donated.
There are a host of potential markers that will allow for more thorough characterization of multiple cell types, including T cells (CD4 and CD8 and their many subtypes – naïve, memory, etc.), T-regulatory cells, natural killer cells, monocytes, dendritic cells, and others.
Dr. Chung is currently using blood and bone marrow samples from Memorial Sloan Kettering patients because he can follow their myeloma responses and relapses in the clinic and see correlations. He can also see how patients trend over time. In addition, Dr. Chung is analyzing samples from the STAMINA trial, comparing patients who relapsed post-transplant within two years with those who have remained in remission at least 4 years post-transplant. He is also reviewing immune function after transplant. Some immune cells do “reset” after transplant, but what is the quality of those cells? It’s not just a quantitative (how many immune cells) issue, but a qualitative (how strong are these cells) issue as well.
The lessons Dr. Chung has learned thus far indicate that patients with a more dysfunctional immune system do not do as well and may not respond optimally to immune-based treatment. For example, the current CAR T therapies use a patient’s own T cells as the starting material. But if that is weak to begin with, the outcome may not be as strong or as long-lasting compared with patients with strong T cells, thus in part explaining relapse early following CAR T treatment.
Dr. Chung’s overarching goals are to:
- Identify immune system profiles indicative of “immune fitness” that could help risk stratify patients
- Use these profiles to predict how well a patient will respond to therapy (especially immune-based) before the treatment is given
Your donations to the Myeloma Crowd Research Initiative will help this important work progress with deeper analysis on more patient samples. Absolutely 100% of all funds donated to the MCRI are given directly to the researchers. Please consider donating to this important project today.
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