Friday, the first day of the 64th Annual American Society of Hematology (ASH) Annual Meeting, is symposia day. I attended the IMF’s Satellite Symposium, “A Conversation with the Myeloma Experts: Making Sense of the Evolving Treatment Landscape.” The experts were the following: Dr. S. Vincent Rajkumar (moderator; Mayo Clinic—Rochester, MN); Dr. Shaji Kumar (Mayo Clinic—Rochester, MN); Dr. Yi Lin (Mayo Clinic—Rochester, MN); Dr. Thomas Martin (University of California at San Francisco); Dr. Phillippe Moreau (University of Nantes—Nantes, France); and Dr. Jesus San-Miguel (University of Navarra— Navarra, Spain).

While the panelists discussed the various myeloma disease states, I’m going to focus on what I learned from the first topic, which was, “How do you determine risk of progression for smoldering multiple myeloma (SMM), and when do you consider therapy for patients with SMM?” Dr. San Miguel was the lead presenter on this topic. My summary, from a patient perspective, includes the following:

How do you determine risk of progression for smoldering myeloma?

  • Given the rate of smoldering multiple myeloma (SMM) (0.5% in those over 40 years old), finding a cure or at least a way to delay progression at this state of the disease would be beneficial, as it would decrease the number of patients with active disease.
  • When a patient is diagnosed with SMM, it’s important to find that patient’s risk of progression.
    • Risk of progression can be determined through the use of models. The current model most cited is the IMWG 2/20/20 model, which is used to predict progression to active myeloma within two years. Note: this is not a model to indicate treatment initiation, but instead predicts risk of progression within two years. I think this is important because it gives those who are high-risk at least a window of time to learn more and make decisions.
      • Dr. San Miguel shared a 2/20/20.02 model which uses circulating tumor cells instead of bone marrow biopsy. If this model takes hold, it will reduce the unpleasant bone marrow biopsy experience for SMM patients.
  • Patients should be informed by their doctors of their risk of progression, and all options available to them should be clearly discussed in plain language. Patient-physician shared decision-making is vital.
    • Dr. Rajkumar shared that typically 30% of newly diagnosed SMM patients fall in the high-risk cohort.

When do you consider therapy for patients with SMM?

  • Watching and waiting has historically been the standard of care for SMM patients, with regular (typically quarterly) follow-ups to ascertain any disease progression, as evidenced by CRAB criteria.
    • Not treating means the patient avoids the risk of being harmed by potential toxicities and possible clonal selection issues.
  • The rationale for beginning treatment with high risk SMM patients is two-fold: (a) to delay progression, and/or (b) to cure.
    • Determining the evolving pattern of key lab values is important (e.g., 2/20/20.02). This includes:
      • The presence of Bence-Jones proteins (>500 mg/24 hr is associated with time to progression (TTP) of about 1 year)
      • The presence of circulating plasma cells (more than 2.0% is associated with TTP of about 1 year)
      • High-risk cytogenetics
      • Genomic profiling
      • Focal lesions
      • Positive PET without lesions
    • Dr. Kumar indicated the importance of looking at the patient in front of you and not just scoring systems and numbers.
    • An analogy that Dr. Martin used is paraphrased as “It’s best to look at the movie rather than a snapshot.” While looking at the movie, is there an emerging trend or not? If there is, then it is time to start talking about treatment.
      • The advantage of looking for trends, from a patient perspective, is that most patients will likely have time to think about their diagnosis generally, think about their options, and learn about the disease state itself. It seems there would be very few instances where a patient diagnosed with SMM would need to rush into treatment.
  • While there are ~70 trials in, key trials exploring early treatment include GEM-CESAR and ASCENT.
    • These trials, and others, are finding positive outcomes thus far, but they are beyond the scope of this blog to cover in detail.
  • As Dr. Rajkumar pointed out, minimal residual disease (MRD) is used as a marker of treatment effectiveness since it will take years and maybe decades to determine the impact of overall survival (OS).

In summary, this session highlighted the exciting research that is occurring in the SMM space. For fellow SMM patients, my advice is that you take the opportunity you have (in the way of time) to become educated about the specifics of your disease, and then consult with your doctor and perhaps get other opinions about what you think is the best course of action for you. Also, find others with SMM to talk with as that can be very helpful. As quickly as the landscape is evolving in SMM, it’s also a slow process as evidenced by Dr. Rajkumar’s statement that it will take years to determine impact on OS. But we will get there, and I’m so grateful to all the brilliant minds studying this…thank you!