Smoldering Myeloma: Treatment and Risk Stratification



Sagar Lonial, MD, FACP: Given the vast number of FDA-approved multidrug regimens for the treatment of multiple myeloma, how do we approach the individual needs of each patient to obtain optimal and durable responses for those with both newly diagnosed disease and relapsed multiple myeloma?

In this OncLive Peer Exchange® panel discussion, “Navigating Evolving Therapy Choice in Multiple Myeloma,” my colleagues and I will review new data from ASCO [the American Society of Clinical Oncology Annual Meeting in] 2019 to shed light on how to improve outcomes for our patients. I am Dr Sagar Lonial, chief medical officer of the Winship Cancer Institute of Emory University, and I’m also the Anne and Bernard Gray Family Chair in Cancer and the professor and chair of the Department of Hematology and Medical Oncology at Emory University School of Medicine in Atlanta, Georgia.

Participating today on our panel are Dr Amrita Krishnan, director of the Judy and Bernard Briskin Center for Multiple Myeloma Research, and professor in the Department of Hematology and Hematopoietic Cell Transplantation at the City of Hope Comprehensive Cancer Center in Duarte, California; Dr Thomas Martin, a clinical professor of medicine in the Adult Leukemia and Bone Marrow Transplantation Program, an associate director of the Myeloma Program, and co-leader of the Hematopoietic Malignancies Program at the UCSF Helen Diller Family Comprehensive Cancer Center, in San Francisco, California; Dr. Krina Patel, an assistant professor in the Department of Lymphoma and Myeloma, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center, in Houston, Texas; and Dr. Saad Usmani, a clinical professor of medicine at the University of North Carolina at Chapel Hill School of Medicine, and the chief of the Plasma Cell Disorders Program and director of Clinical Research in the Hematologic Malignancies at Levine Cancer Institute in Charlotte, North Carolina. Thank you for joining us. Let’s begin. Welcome.

Let’s start off talking about smoldering myeloma. There was a lot of really interesting discussion on smoldering myeloma. How do we make decisions, Krina? Perhaps you’ll get us started on treatment, observation? How do you frame that paradigm?

Krina K. Patel, MD, MSc: I guess before today, for the majority of my patients who come to me with smoldering myeloma, mostly it’s observation or clinical trials. If we have clinical trials for high-risk patients, usually we’ll put them on clinical trial. I think the questions are toxicity versus any efficacy. Most of my patients want something to be done because they know they have cancer. But if you talk to them and say, “Well, this is something we can observe and probably watch because, I don’t know I can make your life longer by treating,” they are excited that I cannot do any treatment, right? I don’t have to have adverse events, potentially. And so that’s I think the biggest struggle. Do I do something that’s going to help in the future, or do I just watch it? And I think it depends on the patient.

I have some patients who are very savvy, and even if they have a progression-free survival, they want something. I think those are the patients I tend to make sure I put on clinical trials, and maybe those are the patients, based on our discussion later, who I will treat. I think another group would be older patients. If they’re 80 years old and have a little bit of M protein [myeloma protein], their creatinine is 1.2 mg/dL, and I don’t want them to have renal failure, maybe that’s the patient who I would treat with Revlimid or something a little bit simpler to avoid organ damage. But if I have younger patients, I think I have a hard time, without a clinical trial, saying, “Oh, all my high-risk patients should definitely be on some type of therapy,” especially intermediate or low-risk smoldering patients.

Sagar Lonial, MD, FACP: Tom, let’s talk about before ASCO 2019. What was on the menu of things that one could do if you were worried about risk of progression or organ failure in a borderline smoldering patient?

Thomas G. Martin, MD: Well, I would say first off, the things that people should do is not look at the snapshot the first time you see somebody and take what their M protein is or what their bone marrow plasma cells are, what the free-light chain ratio shows, and decide at that point in time to treat people. I do think with all patients with smoldering myeloma, we have to look at the movie—whether the movie is 3 months, 6 months, 9 months, or 12 months of evaluation—to try to find out if this is somebody who you think is progressing or will progress and how high is their risk of developing these organ-damage phenomena.

In my personal practice, I look at the movie in everybody. I think we’re hearing a lot of different ways to treat these patients. We’ll talk about lenalidomide alone; lenalidomide plus dexamethasone; carfilzomib, lenalidomide, and dexamethasone; and a transplant and maintenance and further therapy for several years. I would caution everybody right now because I don’t know we know what the best therapy is. I think if people are going to be at risk for progression, we should treat them as we would treat a patient with multiple myeloma.

Sagar Lonial, MD, FACP: The movie analogy is very Southern California of you. Saad, we heard some new discussions at this meeting on ways to risk stratify that smoldering patient population and perhaps other ways to stratify patients in general based on biomarkers. Do you want to give us a little bit of information on that?

Saad Z. Usmani, MD, FACP: Sure, Sagar. I’m going to actually piggyback on what Tom said. I think we’ve struggled with how best to stratify patients within the smoldering myeloma situation. We’ve attempted to do this in a snapshot way, looking at bone marrow plasmacytosis, M spike [myeloma gamma globulin] value, and light-chain ratios. I have to say, I was a little disappointed in the data that were shared today in the Jesus San Miguel effort. This effort started almost 2 years ago, collecting data from all over the world and major myeloma centers. And it’s probably the largest cohort of smoldering myeloma patients that has been collected, over 2000 patients. I think the initial intent was to look at not just those static time points but to see the dynamics of how patients actually progress from the smoldering myeloma to active disease. And I think some of my critique is on that.

So, based on ROC [receiver operating characteristic] analyses, the group did come up with 3 risk factors—an M spike of 2 g/dL, involved light-chain ratio of 20, and bone marrow plasmacytosis of 20% or higher—and then stratified patients to high, intermediate, or low risk based on those 3 features, and did that successfully. But it still doesn’t answer the dynamics of how these numbers move. I’m still struggling with how to reconcile that.

Sagar Lonial, MD, FACP: Saad, what about looking at BCMA [B-cell maturation antigen] or other biomarkers as predictors of that transition from smoldering to symptomatic disease?

Saad Z. Usmani, MD, FACP: I think looking at those biomarkers is going to be important. I think you’re alluding to the Angela Dispenzieri study that looked at serum BCMA levels in MGUS [monoclonal gammopathy of undetermined significance], smoldering, and active myeloma patients. Again, with ROC curve analyses they deemed that the 75 ng/dL or higher serum BCMA levels correlated with that progression. And patients who had a lower serum BCMA level, they were true MGUS patients. I think incorporating those biomarkers along with cytogenetic data that inform us about disease biology are going to be important in overall risk stratification.

Transcript Edited for Clarity

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