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Home Leukemia & Lymphoma Society HIGHLIGHTS FROM THE MARCH 2021 LLS PODCAST FOR HEALTHCARE PROFESSIONALS

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HIGHLIGHTS FROM THE MARCH 2021 LLS PODCAST FOR HEALTHCARE PROFESSIONALS

Treating Blood Cancers: The LLS Podcast Series for Professionals provides up-to-date and accurate information on diagnosis, treatment, and survivorship considerations to educate healthcare professionals treating patients with blood cancer. Each month, Dr. Ken Miller, a medical oncologist and hematologist affiliated with the University of Maryland Midtown Medical Center and Sinai Hospital of Baltimore, and Leukemia & Lymphoma Society (LLS) volunteer, interviews key opinion leaders on a range of blood cancer topics to help provide a better understanding of these diseases, as well as addressing the importance of clinical trials, side effects management, psychosocial concerns, and survivorship.

In recognition of Multiple Myeloma Awareness Month (March), Dr. Miller sat down with Dr. Edward Stadtmauer, section chief of Hematologic Malignancies; Roseman, Tarte, Harrow, and Shaffer Families’ President’s Distinguished Professor, Hematology-Oncology Division; Perelman Center for Advanced Medicine at the University of Pennsylvania. Dr. Miller and Dr. Stadtmauer discussed new and emerging treatment options and more. Here are some highlights from this episode.

Dr. Miller: This has been an incredibly exciting time for clinicians treating patients with myeloma because there’s a feeling that we can do so much more than ever in the past. Thirty years ago, treatment was really melphalan and prednisone, and survival was very short. Thankfully we have more and more patients living for years and decades. So how has our understanding changed in the last decade or two?

Dr. Stadtmauer: The last 30 years or so have been a revolution in our understanding and our treatment for all blood cancers and particularly multiple myeloma. … When we first were studying myeloma, we thought of it as maybe a single clone of cells. And now we know that probably from the diagnosis, from the initial presentation of myeloma, there are numerous clones of these abnormal plasma cells. In many ways one of them dominates at any given time in the natural history of myeloma. But it really becomes sort of a game of whack-a-mole, where the initial therapy gets rid of one clone, but then frequently there’s another clone that then starts proliferating with different characteristics and potentially different sensitivities to therapy. … The other major area we focus so much on is the malignant plasma cells, but they are growing in an environment, a microenvironment of the bone marrow, that we’re really just starting to understand. And it is that interaction between the microenvironment of the bone marrow and the other lymphocytes and myeloid cells and cytokines that either makes an environment that is conducive to these malignant plasma cells growing or can be inhibitory, and a lot of our work is trying to make the environment more hostile for these plasma cells to grow.

Dr. Miller: In light of what you were talking about, the microenvironment and the interaction between that and the plasma cells, how do you look at the phenomena of monoclonal gammopathy of undetermined significance (MGUS)? Do patients have an MGUS versus transforming into myeloma because of something to do with their microenvironment or their immune system?

Dr. Stadtmauer: This is a very important area of investigation, and I think there’s definitely an interaction between malignant plasma cells in the microenvironment [and] smoldering myeloma, where patients can sometimes smolder, meaning that they have greater than 10% malignant plasma cells in their bone marrow and usually monoclonal protein, but don’t have the other manifestations of lytic bone lesions and cytopenias and renal insufficiency. These patients can sometimes smolder for years and sometimes for decades, and I do believe that it is because of the sort of “yin and yang,” and the interaction between these malignant plasma cells and the microenvironment, particularly the immune environment that the cells are living in, that keep them in that steady state. It’s usually either some disruption of the microenvironment or further clonal evolution of the malignant plasma cells that then leads to that switch to a more malignant disease.

Dr. Miller: I wanted to ask you about the goals of therapy. If a patient asked you, and sometimes they ask, “Can this be cured? Can my disease be cured?” How do you respond?

Dr. Stadtmauer: I’m still a believer that I consider myeloma a chronic illness, just like chronic myeloid leukemia, where patients have an excellent chance. In fact, I think that the initial therapy for myeloma is one of the medical miracles of the past 20 years. Twenty years ago we were hopeful that maybe half of the patients would respond to therapy and patients would live with the disease for a number of years. Now we expect 90% to 95% of people to respond to therapy, and people live for decades with the disease. So, we certainly expect the patients to respond and go into remission. The problem is getting rid of every last abnormal plasma cell. However, we do believe that there is a subset of patients who are what we call “functionally cured,” patients who decades later maybe not on anything and not relapsing. Then those people are probably functionally cured. My goal is long-term survival.

To listen to the entire conversation and other podcast episodes, visit www.LLS.org/HCPpodcast.

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