Optimizing Treatment for MM: Transplant and Maintenance

A. Keith Stewart, MB, ChB: For younger, fit patients, autologous stem cell transplant remains a standard of care. Recent studies have challenged that notion by seeing if combinations of new modern drugs can replace the need for autologous transplant, which is still a quite toxic and inconvenient regimen for most of our patients. It can take 2 weeks in the hospital and a number of months to recover. Unfortunately for patients, and I think for all of us, the role of the transplant was cemented by those trials. They continue to show an advantage for patients having transplants, who tended to live longer and be in remission longer from their disease. So, for the time being, autologous transplant remains a cornerstone of our treatment, particularly in younger, fitter, healthier patients. But some patients even into their 70s can still tolerate that therapy.

The use of lenalidomide maintenance after induction therapy and after stem cell transplant has become, finally, generally accepted worldwide. Multiple phase III trials and multiple MET analysis have shown that using lower dosages of lenalidomide continuously over many years can reduce the risk of recurrence of multiple myeloma with relatively modest, if not negligible, toxicity for many patients.

So, this has become a standard of care in the younger patient, to be employed posttransplant, and in the elderly patient with a more continuous therapy approach from time of diagnosis; uninterrupted use of lenalidomide in this setting. We’re beginning to see other drugs employed in there—ixazomib and potentially daratumumab will also perhaps be used as maintenance therapies. All these trials have shown that patients tend to live longer with better quality of life when maintenance is applied.

It’s not really clear how long it needs to be given for. Many studies use the drug until time of progression, which could be many years. Some studies, particularly in Europe, have capped the number of years, such as 1 or 2 years of maintenance therapy. Practically speaking, for most people, maintenance tends to run to 2 to 3 years in duration.

For patients who develop side effects, of course we have to dosage reduce or even stop. If we have to stop there, perhaps there are other drugs that we could employ. But we tend to use toxicity or things like fatigue or diarrhea as reasons to discontinue therapy. These drugs, particularly lenalidomide, have been associated with a slight increase in second cancers, particularly of the bone marrow. And because of that, we are also quite wary and watchful of the bloods of a patient. If we start to see that they are perhaps trending downward, it can be another indication that it’s maybe time to take break.

The use of MRD testing, or minimal residual disease testing, is rapidly becoming part of the arsenal we use to make those decisions about whether to escalate therapy or de-escalate. So, many academic centers today, after a year or two of maintenance therapy, will perform MRD testing and use that as a decision point for whether to discontinue the drug or continue, or even add to it if the test is going in the wrong direction. MRD testing is still not generally quite used in a widespread fashion outside academic centers, so it does remain a rather niche tool for now as we learn more.