How Close Is the IMF to Curing and Preventing Myeloma? 

This week's "Ask Dr. Durie" comes from a patient who wants to know how close are we to achieving a cure or to be able to prevent myeloma? Very, very excellent question. And I think that the first thing to be aware of is that it does take time to document if a patient has been cured or not. 

Right now, we are achieving really excellent results with what we call MRD-negativity after a decisive initial therapy using combination therapy. But the question is how long will that MRD negative last? And is a patient cured? Will the myeloma ever come back? And unfortunately, we're stuck with the problem that it'll take time for us to know that. We've already followed patients to ten years and 20 years. 

And so, we know that patients can do well for these two decades. But sometimes there can still be a low level of myeloma that can relapse later. And so, I think a better target for discussion is can we achieve long-term survival for myeloma with good quality of life? And this, in my mind, is very much an achievable goal, one that we are achieving right now. 

Two attempted cure trials have been completed right now, one in Spain, the CESAR trial, using the combination of Kyprolis, REVLIMID and dex plus autologous stem cell transplant (ASCT) with follow up out to 6-to-7 years. About half of these patients are continuing with no evidence of disease— MRD negative and surviving nicely. Over 90% of the patients in this study are still alive and doing well. 

And a second cure trial conducted in the U.S., the ASCENT trial, patients received daratumumab KRd, and likewise have had excellent results. This is in patients who had high-risk smoldering myeloma, the very, very earliest stages of active disease. In this study, 84% of the patients have achieved an MRD-negative status. In this case, out to three years. 

So, how close are we to curing myeloma? Well, we are achieving long-term survival and excellent quality of life, certainly out into this 3-to-7 year range with these current protocols. And we're expecting this benefit to continue. And we are also expecting that new cure trials can add to that level of benefit. 

As far as prevention from our studies in Iceland, we are detecting evidence of monoclonal protein very early at the stages of MGUS and early smoldering myeloma. In this situation, we have the opportunity to understand both what is triggering the initial MGUS that can lead to myeloma and also what is triggering the progression from MGUS to smoldering to active myeloma. And so, in this setting, by understanding, particularly at an immunologic level, the immune system of the patient, by studying that, we can see what factors are leading to the first development of the MGUS and are predisposing to a progression of the disease. And so, there are opportunities to introduce strategies for prevention. 

So, BOTTOM LINE, both in the area of cure and prevention, we are really making solid, active progress. And I'm optimistic in not too many years that we will be able to document even longer, MRD-negative survival and the ability to prevent either the onset of MGUS or the progression to more active phases of disease.