Over the weekend, I attended numerous multiple myeloma talks in the basic and translational science sessions. Translational research is a term used to describe converting basic science research to results that directly help humans, leading to new therapies. Often the phrase, “From Bench to Bedside” is used to describe the goal of this type of research, but I really dislike this phrase. The goal should be to get the patient beyond the bedside, back into the world, living their best life. In my last blog, I discussed the fast pace of research and how it’s transforming the lives of multiple myeloma patients. While progress in therapeutic development has been incredible, some patients do not readily respond to treatment, and most patients eventually relapse. It has been hopeful to see so many talks focused on trying to understand the underlying biology of relapse to ensure that therapies continue to be developed and optimized to improve outcomes for all patients.
Often translational research involves using patient samples to understand the underlying biology of disease and response to therapy. One fascinating area of research is the tumor microenvironment (TME), which is the ecosystem of various molecular, cellular, and structural components that surround the myeloma tumor cells. By learning more about the TME, it may be possible to use combination therapies that target both the TME and the myeloma plasma cells. One new thing that I learned, which is somewhat concerning as a myeloma patient, is a high ratio of neutrophils to T cells is associated with poorer progression-free survival, at least in newly diagnosed patients. My current line of therapy causes a decrease in my absolute neutrophil count (ANC), requiring monthly shots of growth colony-stimulating factors to boost my ANC. I can’t help but wonder if this may ultimately contribute to time to relapse (not to mention quality of life with the bone pain and headaches I get), and I plan to have a conversation with my multiple myeloma specialist to discuss the potential risks of aggressive therapy to avoid relapse that may also impact the health of the bone marrow niche and that may affect quality of life.
Immunotherapies like CAR T-cell therapy and bispecific antibodies have been game changers in multiple myeloma, even though some patients do not respond to these therapies or relapse after only a short time. I’m incredibly grateful for all myeloma patients who have donated bone marrow or peripheral blood samples as part of research and clinical trials to help correlate disease stage with changes in underlying biology. By using a variety of cutting-edge techniques, including single-cell RNA sequencing, next-generation flow cytometry, mass spec technologies, and high-resolution imaging techniques, researchers are learning a lot about the composition of the immune cells in the TME at various stages of myeloma progression to sort out how disruptions in the immune cell composition impact both the progression of myeloma and the response to therapy. Results from studies like these are leading to hypotheses on mechanisms of relapse that can be tested in cellular and mouse models of myeloma to inform new clinical trials to identify novel therapeutic targets or combinations of therapies to address this unmet need.
At our #IMFASH23 International Myeloma Foundation support group leaders blogging team meeting this morning, one of our team members was commenting on how research answers questions and in the process creates new questions to be answered. How wonderful to see so many amazing scientists and myeloma specialists working so hard to find answers to new questions that will continue to help treat myeloma patients so they can move beyond managing myeloma to celebrating the gift of each day, month, and year ahead!
— Jill Zitzewitz, PhD
Follow me on X @JillZitzewitz
Support Group Website: Central MA Multiple Myeloma Support Group