EMN 2021 | Early SMM intervention may curtail progression

So, I think the area of smoldering multiple myeloma is really a pretty hot topic in myeloma right now as well. We now have several Phase III randomized studies that have demonstrated that early intervention offers significant benefit compared to continued observation, particularly in the highest risk group of patients. And so, I think the real controversy currently is also about the intensity of therapy.

The original study that was from Marivi Mateos from the Spanish group, looked at len-dex versus observation. The ECOG study that I published a year or so ago was about single agent len versus observation, but we now have many trials looking at more intensive myeloma-like therapy, whether it’s KRd, whether it’s the GEM-CESAR trial, which uses KRd followed by transplant followed by lenalidomide maintenance. And what I think is clear from those more intensive myeloma-like treatments, is that you can achieve deeper responses.

It’s not clear whether those responses are necessarily more durable. And the reason I say that is the three-year time to develop myeloma in the ECOG trial was 91%. The three-year time to develop myeloma in the GEM-CESAR trial was 92%. So, they’re basically identical, despite the fact that one is giving one drug and the other is giving lots of drugs for a long period of time.

So, I think the jury is out about the intensity that’s needed for therapy. I think that the prevention approach certainly has two large, randomized trials supporting its use. And I think the other part of this discussion is about the easiest methods for risk stratification. I think the 20/2/20 criteria are probably the easiest, most user-friendly criteria that we have in 2021. They will probably evolve in the next few years. But using 2021, the highest risk group of patients, I think, should have a reasonable discussion about therapy on a trial or early intervention off of a trial, or observation if the patient declines the early intervention approach.