DR LOVE: Let’s talk a little bit about a couple of publications. And again, we saw this paper from the Mateos study. Can you talk about what they looked at there, what they’ve seen?

DR RAJE: This is obviously a follow-up study to what was published in The New England Journal of Medicine now a few years back. And what Maria V Mateos did out here was randomize patients with the way we defined smoldering multiple myeloma at that given time, which is the presence of a monoclonal protein, presence of bone marrow plasmacytosis of more than 10% and we were still using things like skeletal surveys at that time. And that is a definition which we’ve used for more than 30 years now.

And what was seen out here was patients were randomized to receive lenalidomide and dexamethasone versus the others were observed, which was considered the standard of care at that time. And what was seen, which was not surprising, is that the progression-free survival was obviously in favor of patients who got lenalidomide and dexamethasone.

DR LOVE: Progression clinically?

DR RAJE: Clinically, as well as by the parameters that we have for myeloma. More importantly, I think what was very striking about this data was that there was a survival difference. And this really got, I think, all of us in the myeloma community thinking. And this is where I think is the biggest teaching from this QuiRedex study, which has now been presented in the Lancet Oncology as a follow-up — the Lancet Oncology follow-up study just shows that early intervention maintains the kind of responses you’d had earlier on. To me, what was most powerful about this study was us looking at this data and then recalibrating on how does one diagnose symptomatic multiple myeloma. Because in 2016, if your standard of care for this patient population is watchful waiting, there should not be a survival difference.

And this is where we came up with the new diagnostic criteria for symptomatic multiple myeloma, maybe even incorporated more specific imaging, like the MRIs, like the CAT scans and the PET scans, and then incorporating light chains in everybody. And we’ve also included the bone marrow cutoff of more than 60% as considered to be symptomatic and treat as myeloma. So I do think it was very instructive. It allowed us to recalibrate and rediagnose what symptomatic myeloma should be. And those are the folks who would be treated anyway as myeloma and not as smoldering myeloma.

As far as smoldering myeloma is concerned, I do think, even in 2000 — despite all of those data — if we now define smoldering myeloma by the criteria we have in 2016, it is still a space where the standard of care is watchful waiting. But it’s important to recognize that you have to do all the other testing. You have to do the more specific imaging. You have to make sure you’ve done the serum free light chain assay. And, as Rafael has said, you have to follow these patients in time because a lot of times the diagnosis of smoldering myeloma is a retrospective diagnosis. And I can argue with Rafael and say, “The fact that his M protein is rising, is this really smoldering myeloma or is this very early symptomatic myeloma?”

DR LOVE: Just to clarify, though, in this original QuiRedex study, what fraction of those patients today would be considered to have myeloma?

DR FONSECA: Well, I think that we don’t have the actual number. We suspect a number of them, because they were considered high-risk by the Spanish criteria, would fall into what we would call myeloma nowadays. So I think the revised criteria fixes some of that gap, but we must know what is the actual difference in those numbers. Do you know of anyone who’s actually published? What I would presume, at least 70% of the ones that went into that study might fall into the new criteria.

DR LOVE: Interesting.

DR FONSECA: I don't know that for a fact.

DR LOVE: And now, you mentioned the ECOG trial this lady might consider. Are their criteria now up to date, the trial itself? Did they revise their criteria?

DR FONSECA: Well, the trial was designed a few years back, so it’s somewhat still in that mentality. If I was to design a new trial nowadays, I would incorporate all of what we know from the QuiRedex trial. I would say that the one thing we’re missing is the kinetics. And people in CLL know this a lot better than we do, the time to duplication of white blood cell count. I think the time of increase for immunoglobulins or free light chains probably is just as important as a marker.

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