Treatment of NDMM has dramatically evolved in the last decade with emerging data from large RCT’s. In this segment of the MM Discussion series CARE™ Hematology Faculty members, Dr. Darrell White (Dalhousie University) and Nizar Bahlis (University of Calgary), discuss how recent data will impact treatment decisions in NDMM and what else is on the horizon that we should be watching for.
How has recent data with novel therapy options/combos changed your approach in the transplant-eligible population?
- Evidence has confirmed that we should be using a proteasome inhibitor in combination with an immunomodulator with transplant followed by Revlimid maintenance
- The question with maintenance moving forward is whether we can add to this to improve outcomes further
- Some of the novel agents investigated in transplant ineligible patients are starting to show similar survival to that which is seen in patients who do get a transplant
- When determining eligibility for transplant we have moved from using an age-based exclusion to exclusion based on fitness and willingness.
Have you become more comfortable offering a patient a deferred transplant approach?
- Recently we have used this approach with a few patients who specifically asked for it, although it is not a mainstream option as of now.
What are your thoughts on the potential to stop treatment based on MRD negativity?
- The MASTER trial was provocative in its design and provided support/rationale for this approach.
- Other recent trials (incl. FORTE, CASSIOPEIA, etc.) indicate that patients who come off therapy can have sustained MRD negativity.
- We will know more in the next couple of years. What MRD analysis we will use is debated.
How has recent data with novel therapy options/combos changed your approach in the transplant-ineligible population?
- Change in practice in Canada has been remarkable in the last 15 years.
- The shift at the moment is toward RVD (lite).
- Results from the MAIA trial showing a potential median PFS beyond 60 months with DRd demonstrate how outcomes continue to drastically improve with novel regimens.
What is coming next in the pipeline that you are most excited about?
- Most exciting trials with immune therapeutic approaches (CAR T, T-cell engagers, NK-cell engagers, etc.) are in later lines.
- It will be interesting to see how these fare in earlier lines.
- Precision medicine (update from the BELLINI Trial).
- We can see the future on MM treatment being completely chemotherapy free.
Do you see us treating MGUS in the future? Do you see smoldering MM disappearing into either MGUS or myeloma?
- Research is being done so we can better predict patients from the smoldering group who are likely to progress to myeloma in the near future. These are the patients that will benefit from earlier treatment.
- Greater understanding of the biology of MGUS will help provide clarity on best practices for screening family members (and how often).
- It is a very exciting time and we can be fairly confident that one day MM will largely be considered a curable disease for most patients.