As I mentioned in my previous blog, the uncertainties of living with smoldering multiple myeloma (SMM) can be whittled down to two “million dollar” questions: (a) “Will I progress to active disease?” and (b) “Should I consider treatment, and if so, how and when?” This blog is dedicated to the second question, “Should I consider treatment, and if so, how and when?” Updates to ongoing studies examining this question were presented at the 64th Annual American Society of Hematology (ASH) Annual Meeting.

This question includes a lot of nuances, and I’ll acknowledge from the start that this blog probably won’t do the topic justice. But my goal is to highlight the latest information from ASH that addresses this question, and also pose some “points to ponder.” Most studies looking at treating SMM are focused on high-risk SMM (HRSMM), often defined by the 2/20/20 criteria or the PETHEMA criteria, so it’s important to keep this in mind.

Sigrun Thorsteinsdottir, MD, PhD, from the iStopMM project gave an excellent overview of SMM and highlighted the various perspectives by leaders in our field regarding treating HRSMM (See The Consultant’s Guide to Smoldering Multiple Myeloma). And while there has been much research and progress is being made, several points remained unanswered. These include:

  • Improving risk stratification, including more effective dynamic models.
  • Trials need endpoints that are meaningful to patients, things like quality of life while on treatment and overall survival. (Note, a few discussions at ASH addressed the rational for the current endpoints, and a key outcome of this is that it will take a long time, maybe 10 or 15 years, to accurately assess overall survival. The current endpoints at least allow researchers to “move the dial forward,” so to say, to get closer to the ultimate goal.)
  • What type of treatment will be best, given that those with HRSMM haven’t yet displayed SLiM CRAB criteria? Is a one or two drug combination effective, or something stronger like a three or four combination?
    • When giving lenalidomide, some risks are known, including the chance of secondary cancer development.

While many trials are taking place to examine SMM treatment, two high-profile trials with updates presented at ASH are the GEM-CESAR trial and the ASCENT trial. In the GEM-CESAR trial (ASH Abstract 118), updates include 94% of patients are alive and progression-free at the median follow up of just over 5 years; 6 patients progressed to MM and 7 patients died. Moreover, 23% of HRSMM patients treated have maintained MRD negative status 4 years post autologous stem cell transplant and 2 years after finishing the treatment.

In the ASCENT trial (ASH Abstract 757), updates include that the quad therapy given for 2 years was associated with high response rates and deep response rates of MRD negative status. 55% of the patients have completed the 2-year regimen (carfilzomib, daratumumab, lenalidomide, and dexamethasone with induction for 6 months, consolidation for 6 months, and maintenance for 12 months). Thirty-one percent of the patients are still in treatment while 14% of the patients left the study (3 withdrew, 3 experienced adverse events, 3 were by physician decision, 2 were due to progression, and 1 died).

There is a lot happening, and as I think back over the past 6 years since my diagnosis, the changes and research updates in the smoldering space have been astounding. Despite that, it will still be 10 or 15 years, or more, before we know how these trials have impacted those with HRSMM. I’ll leave you with some points to ponder, as you consider the question, “Should I consider treatment, and if so, how and when?”

Thank you for reading, and thank you to all of the researchers who are diligently working to help provide answers to the million dollar question: “Should I consider treatment, and if so, how and when?”.

Jessie Daw
Follow me on Twitter @Daw6Jessie