IMiD Sequencing in Multiple Myeloma - Episode 3

Managing Patients with NDMM

January 10, 2018

A. Keith Stewart, MB, ChB:In the more frail patient, we tend to use an IMiD as our backbone of therapy, most often lenalidomide, combined with dexamethasone or combined, sometimes, in the regimen we call RVd-lite with once-weekly bortezomib and low doses of dexamethasone. We’ll often even start with a lower dose of lenalidomide for tolerability. And that regimen of RVd-lite, or just lenalidomide and dexamethasone alone, are our usual choices of therapy in the elderly patient. I think we will see data emerging in the next 12 months. In fact, at this meeting, we’re seeing data emerging, that the addition of the monoclonal antibody daratumumab can also improve outcomes in these patients with minimal toxicity. And I think this lenalidomide/dexamethasone with daratumumab may well become the de facto standard within the next year or 2 for these more frail patients.

Recent data, particularly from the Myeloma Study Group in the United Kingdom, I think have provided a final level of evidence we need to conclude that lenalidomide maintenance, or lenalidomide continuous therapy, is the treatment of choice for all myeloma patients. In the United States, that has become the standard, but I think around the world, it will now also become commonplace.

Having said that, I think there are other patients who lenalidomide maintenance alone may not be enough, that we do need to layer on a proteasome inhibitor, particularly in our high-risk subgroups. The controversy around lenalidomide then is no longer whether to use it or not, it is how long to use it for, and how to manage toxicities or avoid the more serious toxicities that we sometimes see. I think that we still don’t know the answers. We don’t know whether stopping it in 1 year, like they do in France, versus continuing until relapse many, many years later—which is the current recommendation in the United States—is correct, and I think some more study is required.

My own practice is to use these drugs for about 2 years and look at the depth of remission. If patients are in a good and deep remission, I sometimes will stop. If a patient still has evidence of disease, I’m more inclined to continue for at least another year of therapy. I do get a little nervous beyond 3 years about possible myelodysplastic syndrome or other hematologic malignancies. I watch very carefully the platelet count and mean cell volume, and use that sometimes to gauge whether to continue or discontinue those drugs.

We have numerous clinical trials now supporting the use of lenalidomide in the frontline setting as a backbone of therapy. In fact, most of the new drugs are being added to lenalidomide—elotuzumab, daratumumab, ixazomib—and are all maturing and we expect results of those trials soon. What we have been more convinced by recently with some new and very large studies is that these drugs can improve overall survival. They’re useful in both high- and low-risk genetic disease, and they should probably be sustained over longer periods of time as continuous therapy until the time of relapse.

Transcript edited for clarity.