EBMT 2020 | Treatment strategies for smoldering myeloma

Smoldering myeloma is, again, an area of great interest. It’s an area where a lot of research is being done. The idea behind trying to do work in smoldering myeloma is if you want to cure a disease, why not get to it early before it becomes full-blown? And why not prevent the progression to active multiple myeloma which we know, if not treated appropriately, is probably fatal in the majority of patients? I do think that is changing with everything we have available for the care of myeloma patients. So that’s the impetus to want to treat smoldering myeloma. It’s very few diseases like myeloma, which have a precursor disease state, wherein you can identify these patients and then consider treatment.

I think our biggest challenge in the smoldering multiple myeloma space is how do you define high-risk disease? And we have now come up with several different approaches. I think the most recent approach of using the 20-2-20 definition, which the Mayo Clinic and the International myeloma Group has validated. And what it really is, is where you have 20% plasmacytosis, you have two grams of protein, and you have serum-free light chain ratio of 20 or greater. Depending on the number of these risk factors, you can then estimate your rate of progression. So even if patients have all three of these risk factors, your risk of progression is somewhere between 50% and 60%. So even with this really robust and good model, we do find that 40% of patients are actually not going to progress to full-blown myeloma. So even if we include all of these patients in some of the clinical trials which are ongoing, we may be over-treating 40% of patients.

As I’ve mentioned already, there’s a lot of different trials. If you go onto clinicaltrials.gov, you’re going to be overwhelmed with the number of clinical trials which are happening in this space. They’re from the very early non myeloma-like approaches to full-blown treatment, with transplant, full drugs, and so on and so forth. I think they’re still trying to figure out which patients need to be treated.

The data which has recently been presented and now published is the ECOG trial comparing lenalidomide to nothing at all. In that patient population, what you saw was high-risk smoldering myeloma was defined. Again, the problem was the study was done even before the IMWG had the actual new definition of symptomatic active myeloma. So some of the patients included in that trial already had myeloma, but that trial was used and what it showed was a progression-free survival benefit.

I don’t think that should change the standard of care for smoldering multiple myeloma because, as of right now, I still think smoldering multiple myeloma should be a disease where “wait and watch” should be the policy. We should be treating patients only on clinical trials until, and unless, we try and refine our definition of what high-risk disease is. And that’s ongoing work. Once we can really identify, yes, this is a patient who is absolutely 100% of times going to progress to multiple myeloma, then intervening in that patient population will become the standard of care. And we may actually, in fact, change the definition of what smoldering myeloma is. We may actually call these patients active disease and treat them with the best possible approach. Until that happens, we need to continue to do our work in this space. And our work should be around continuing to identify risk factors, to better define who are the ones who will progress and then identify the best possible options.

As of right now, my recommendation would be treat patients with smoldering myeloma in the context of a clinical trial only. Otherwise, the standard of care for a smoldering myeloma patient should continue to remain “watchful waiting.”