Dr. Joseph Mikhael Conducts a Special Q&A on Facebook 

So LW sent us this note and so you, you're asking an extraordinary question actually. So typically in myeloma we're giving treatment whether patients are eligible or not for stem cell transplant influences whether or not we give a transplant. And then they often go on to maintenance therapy and most commonly with the drug Revlimid, generic name lenalidomide. And right now the best evidence we have is to give lenalidomide for at least four to five years. This was even actually just reiterated at a meeting in December where our friends from the UK presented longer term follow up of patients who were given lenalidomide maintenance. And there were still a benefit even in MRD negative or minimal residual disease or some people call it measurable residual disease negativity. Which means we, we can't find any trace of the myeloma typically at least one in a million cells.

We can't detect any myeloma that those patients benefited from at least four to five years of maintenance. But at the five year mark we have to say we don't really know for sure and the myeloma community is a little split on this. There are some who will be purists and say, you know what? We've had patients on maintenance lenalidomide for 7, 10, 12 years, please continue it. Others might say, look, you know, if the disease is under great control for this long, it's reasonable to come off. And so I think it's worth having a conversation. Of course I can't give direct medical advice per se, but it's worth having a conversation with your physician about this exact situation because once people have hit the five years, if it really is as negative as you're describing, if there aren't any what we would call high risk features, which we tend to be nervous about, 'cause that means the disease can come back more quickly, then it may be very legitimate to do that.

And it's really remarkable now with our therapies in myeloma that there are patients that we can do this to. And I would hope that with time we're gonna develop more and more stopping rules, partly helped by the MRD testing or minimal residual disease testing to know if someone has no measurable disease to be able to stop therapy. I say it all the time, I just chatted with a physician right before this call. I said, you know, my favorite therapy in patients is nada, nothing and if we can get more patients on no treatment, that would be very good. So that is a really excellent question and so thank you very much for that.

Oh wow, the questions are pouring in. I better answer them more quickly. Is it possible to detect these circulating DNA in myeloma with MRD negative by using mass spectrometry, I think is what they mean during treatment periods? Well thank you YC for that great question. The short answer is we're working towards that. It's not as easy as we might think. There are some cancers in which instead of having to find the tumor, we can measure tiny bits of DNA that are circulating in the blood that are connected to that cancer.

And sometimes it allows us to see if there's still residual disease, but also to detect an early relapse in some of those solid tumors and other cancers. We're trying to do the same in myeloma and there's some great work going on our colleagues in Australia that have been part of the Black Swan Research Initiative, which is what the research arm of the IMF has been doing, but it's really not completed yet and it's not as simple as that.

There's some work that we do even in the lab that I'm affiliated with here in Phoenix at Tigen looking at not so much the circulating DNA but even just very, very few tiny amounts of circulating plasma cells that can be detected. And that's really quite prognostic. So this is a field that is evolving and I'm gonna suggest has actually become very important because one thing patients don't enjoy is having multiple bone marrows. And so if there's a way to detect the disease in the blood instead of having to do a bone marrow, I think we will want to be doing that and I think we're gonna be doing that more.

So another question from KA I'm interested in the rare types of multiple myeloma, no secretory or probably what they mean is where, where we're not releasing the protein in the blood multiple myeloma, they're asking is there treatment for this? So thank you for a great question.

As I mentioned in the start myeloma is a complicated disease where these plasma cells grow in the bone marrow and they release that bad antibody into the blood and typically the antibody is entirely intact. And we call that an M spike because there's two parts to the antibody, what's called the heavy chain and the light chain. And those are connected and they stay intact. About 20% of patients will only have light chains. The majority of patients actually have both measurable but about 20% have have light chains only. And then there's a tiny fraction of patients, about 1% that have what we call non-secretory myeloma where we can't measure anything, and it's tricky because we don't detect the disease as well as we would typically do in the blood or in the urine.