The Impact of Evolving Treatment Options in Multiple Myeloma, Part 3

Bruce A. Feinberg, DO: Joe, I want to go back to you in addressing some of those issues, what is the ultimate goal? It seems like we just keep adding, but we also don’t take anything away. We’re starting to get better, maybe, measures of success, because in hematological malignancy that’s always been tough. Now we have MRD [minimal residual disease], so maybe you can give us a quick primer on MRD. When does MRD become the determinant? If we go to quadruplet therapy and you get MRD to a certain depth, maybe you don’t go to transplant, or maybe you don’t go to maintenance. How does that all work? It just seems like we’ve been in the additive mode, and that makes sense. I remember almost 2 decades ago when testicular cancer treatment was seen as such a success, thinking maybe we can give less. I’m wondering in myeloma, on the one hand, we’ve given years and years of life to patients, but we’re getting to that point where we start to think about, is it always more? I gave you a lot to deal, with but start with MRD.

Joseph Mikhael, MD: You’ve asked a great question, which is sentinel to the whole discussion. MRD, or minimal residual disease, is a test that we use in other hematological malignancies that we’re just starting to bring into multiple myeloma. I’ll preface the comment by saying, I would strongly caution anyone about using MRD status to make a significant change in treatment right now because we haven’t reached that stage yet. We know it’s prognostic. We know that it can be predictive of both progression-free and overall survival. We haven’t quite reached that stage yet, although I think we’re getting closer to it, Bruce, more than ever. You’re right, we’ve been in this additive stage. More is better, more is better, more is better. But we are starting to think about so-called stopping rules. For example, where can we say someone achieves MRD negativity, maintains it for X period of time and they have low-risk disease, well, now we can deescalate, or maybe even not go on to further maintenance therapy. As opposed to the patient who doesn’t achieve MRD negativity, or the high-risk patient, where we’ve learned that MRD is not exactly the same in 2 patients just because they’ve achieved it. It’s very prognostic and it’s very helpful, but I’m hoping that we will come to a time where it’s not just, “You’ll take this drug, and you’ll like it, forever,” which has been the approach over the last several years. There is a law of diminishing returns, where we’re starting to see some studies showing that quadruplets seem to be better than triplets. But we’re starting to learn, “Oh, maybe you don’t need that fourth drug eternally. Maybe we can start deescalating.”

I know it’s a bit of a vague answer to say we’re still learning it, but we are still learning it. Thankfully, we’re doing prospective studies to answer the exact questions you’re asking. We are starting to hear that although these drugs are more tolerable and are getting people into a deeper and more durable remission, ultimately the path to cure is to get people off treatment. Clearly, that’s the direction we’re moving in, but right now it’s a little too early to put the brakes on just because someone reaches MRD negativity. It’s good prognostically, but it’s a little too early to make big decisions.

Transcript Edited for Clarity