The Tremendous Complexity of Treating RRMM

Joseph Mikhael, MD, MEd, FRCPC, FACP, is chief medical officer of the International Myeloma Foundation, where over the last few years he has led the M-POWER Program, seeking to improve the short- and long-term outcomes of patients who have historically not had great outcomes in multiple myeloma (MM), primarily the African American and Latino American communities. He is also a professor at the Translational Genomics Research Institute in Phoenix, part of the City of Hope system, and directs the myeloma program and research program at the HonorHealth Research Institute in Scottsdale, Arizona.

In this interview from our coverage of the European Hematology Association 2024 Congress, at which he presented, “How I Treat Relapsed/Refractory Multiple Myeloma in Early Lines: The US Experience,” he discusses the complex principles that underlie treating multiple myeloma in the US.

Transcript

Can you discuss the US approach to treating patients with early relapsed/refractory MM?

The treatment of myeloma is complicated, as we know, at all levels: frontline, early relapse, late relapse. But there's been a lot of interest in early relapse of late, especially with the incredible number of phase 3 trials that have guided our thinking and the way we approach patients with early relapse. And I had the privilege here of speaking on this topic, about how is it that I approach patients with early relapse. Obviously, there's tremendous complexity, but I'll simplify it with a few key principles.

I would say principle number 1 is that we don't have a sinkable algorithm, where we say we always treat patients with this, then with that, then with the other. It's much more directed on patient factors, disease factors, based on how the patient is doing, what they've been exposed to before. So it's more of a strategy than just a script of doing it, now that we have multiple options.

Principle number 2 is that we want to introduce new mechanisms of action. We really do have 4 major classes now of drugs: the proteasome inhibitors, the immunomodulatory drugs, the monoclonal antibodies, and now XPO1 inhibitors. And indeed, during my talk, I focused on the data that we have now using selinexor in early relapse, initially in combination with bortezomib, but now really in combination with almost every other myeloma drug we have and with multiple other classes.

I would say principle number 3 is that we want to make sure we don't, if you will, save the best for last. We try to use the best combinations we have early on to get a deep and most durable response when we have access to those therapies because we know that with each line of therapy, there are fewer patients that are available for transplant.

And then lastly, I would say a very important principle is always—as my father taught me when I got accepted to med school—we have 2 ears and 2 mouth for a reason. We have to listen to our patients. We have to constantly be assessing the toxicity a patient is having and dose adjust accordingly. For a lot of our patients, we can deescalate their therapy—in particular, dexamethasone, for example—but very often the other drugs that we're using, perhaps dose reduction or dose delay based on that so that it is sustainable, so that we can have the maximal input.

And with these principles, ultimately we found that we have lots of choices. If someone has not seen a CD38 monoclonal antibody, we classically use a CD38 antibody with either carfilzomib or pomalidomide. If someone has, we may consider another class, like selinexor. If they've not seen carfilzomib or pomalidomide, we often include those. So we do have a lot of choice.

And then very lastly, now just as of April 2024, we now have the opportunity of introducing CAR [chimeric antigen receptor] T-cell therapy in early relapse, even as early as 1 prior line with cilta-cel [ciltacabtagene autoleucel (Carvykti); Janssen/Johnson & Johnson] and 2 prior lines with ide-cel [idecabtagene vicleucel (Abecma); Bristol Myers Squibb and 2seventy bio, Inc], and we tend to be focusing our efforts in those patients and those that have the highest-risk disease or functional high-risk disease. But again, it's another option in our large menu to provide to our patients.