Treating Multiple Myeloma Through Multiple Relapses

A. Keith Stewart, MB, ChB: Obviously as patients experience multiple relapses, the goal of trying to eradicate disease becomes minimal residual disease—perhaps even cure diminishes. And we focus more on quality of life than getting the deepest remission possible. We also have to be cognizant of prior side effects of therapy and the mechanisms of action of drugs. So, when we get to a third or even fourth relapse of the disease, we’re tending to pull for new agents and new targets, although sometimes we can recycle drugs that we’ve used in the past.

Good examples today would be the emergence of BCMA as a target. A lot of excitement around targeting that drug with either an antibody-drug conjugate or what we call BiTEs, or bispecific T-cell engagers, enhancing their function. Or the very exciting area of chimeric antigen receptor T cells, which is emerging rapidly as a very effective and attractive strategy in late-relapse disease.

There are also some new small molecules that we should mention that have emerged as effective in multiple myeloma and late relapse. Again, targeting different genetic targets, one of which is venetoclax. This is a drug that seems to be particularly useful in one type of myeloma, which has a translocation 11;14. But when it is combined with a proteosome inhibitor—and we heard about this in an abstract at this meeting here in Chicago—when it’s combined with carfilzomib or with bortezomib, we see very high response rates with venetoclax in those drugs.

The other drug we should mention is Selinexor. Selinexor is a novel mechanism of action. It’s a completely new class of agent to be used in multiple myeloma, and it seems to be quite effective even in patients who have failed all 5 commonly used drugs. Patients we call penta-refractory. Selinexor has just been reported to have a 25% response rate in those patients. It is orally delivered, so it’s convenient. But it can be a challenging drug for patients. There’s a definite learning curve, and it’s used for the physicians, the nurses, and the patients themselves in finding a tolerable dosage and a way to take it over long periods of time.

So, I guess in summary, we have lots of new drugs coming—BCMA-targeted agents, Selinexor, venetoclax that we can add to the traditional therapies we’ve used in the late-relapsed setting.

Unfortunately, in myeloma, most patients are still not cured. There’s definitely still an unmet need in this disease, despite the plethora of very exciting advances we’ve seen in the past 5 to 10 years. We are seeing the emergence of CAR-T and other T cell—engaging therapies as perhaps the answer to converting deep responses into cures, and we need to learn more about how to use those drugs earlier in the disease course.

I think the future is bright for myeloma patients. Every 2 or 3 years, we have a new drug that extends life and extends survival. And as we begin to learn to how to use those drugs early in the disease course when the disease can still be intercepted and perhaps cured, I think we’re going to start seeing that cure curve and the plateau of long-term survivors increase.