IMiD Sequencing in Multiple Myeloma - Episode 1
A. Keith Stewart, MB, ChB:By definition, patients who have more than 10% plasma cells in the bone marrow, without symptoms, have smoldering myeloma. Recently, we have discovered that there is a group of those patients who will go on to get myeloma more frequently, and we can define that as patients who have more than 60% plasma cells in the bone marrow, a serum-free light chain ratio greater than 100, or the presence on an MRI or PET scan of lytic bone lesion. We feel that those patients, today, should be treated as if they have active myeloma.
At the ASH meeting here in 2017, there were some new abstracts suggesting that genetic factors could also be used to predict who’s going to respond, who could be watched and waitwho could be monitored without treatment—and which patient should probably have treatment today. They include looking at the oncogene calledMYC, and they included some other signatures that have been derived from gene expression profiles. If you do decide, there has been a lot of interest in asking the question, if we take these high-risk smoldering patients, should we treat them or should we continue to watch-and-wait for 2 or 3 years until they get active disease?
There were abstracts at this meeting that described very aggressive approaches to treating smoldering myeloma. But I think the message for community physicians and others watching is that for most cases, we should continue to watch and wait and not treat these patients unless they have some of these new criteria present. We need longer follow-up and clinical trials. And while it’s an exciting concept, it needs to be matured before it becomes part of the standard practice.
The clinical studies that have been presented were using single-agent drugs, like lenalidomide or even daratumumab, initially to treat smoldering myeloma. I think probably a more convincing strategy is to treat these like they have active disease. In fact, the Spanish group at this meeting described using carfilzomib/lenalidomide/dexamethasone, transplant, and then consolidation with the same drugsa very aggressive strategy—to see if you could actually eradicate or cure the disease. If it were my choice and I did choose to treat a smoldering myeloma patient because I was worried about their risk of progression, I would tend to go all in and treat them as if they had active myeloma.
Monitoring patients with myeloma mostly involves choosing blood tests. We use those to monitor the level of the serum monoclonal protein or increasing the serum-free light chain. And we find the serum-free light chain to actually be very helpful. It actually tends to be the thing that changes first. It will go up first and relapse, and it will come down first in patients who are responding. The half-life of the larger monoclonal protein can be quite long and take longer to change.
We usually monitor that every month in patients who are on more of a maintenance strategy. We can move that to every 2 months, but usually not much less frequently than that. For patients who are off treatment, we perhaps move to every 3 months monitoring for convenience for the patient and their family. But one change that this happened recently is the use of minimal residual disease testing. This does require a bone marrow exam so we tend to do that less frequently. Generally speaking, it’s maybe every 6 months or 12 months when we’re looking for minimal residual disease in the bone marrow and whether it changes or not over time.
PET scanning has also become more common. We used to just use skeletal survey as a plain X-ray of all of the bones in the body. Now, we use a much more accurate and sensitive test called PET/CT scanning. This is usually done at diagnosis in multiple decision tree points throughout the treatment course. And the value of that is to pick up disease growing outside of the bone marrow, which has also become more common as our treatments have improved.
Transcript edited for clarity.