Approaching Treatment of Relapsed/Refractory Myeloma


Factors to consider when approaching therapy selection for patients with multiple myeloma disease progression.

Keith Stewart, MD, ChB, MBA: We’re going to turn our attention to the patient who is relapsing, which unfortunately remains a common occurrence in multiple myeloma. We closed our discussion of frontline therapy by talking about minimal residual disease [MRD]. Many of us have started looking at that on a regular basis in our patients. It begs the question, and I’ll start with you, Sagar, what are you using to decide when to restart therapy at relapse? Do you use MRD going from negative to positive? Do you wait for monoclonal protein levels to rise? Do you wait for symptoms? Where are you on that spectrum to date?

Sagar Lonial, MD, FACP: I feel like I’m going to be the old school person on this one. Unless they’re high risk or presented with renal failure, I’ll probably jump on them a little bit earlier. I’m not at the point where MRD-negative to MRD-positive is where I’m intervening. But certainly, I will let people twiddle up on their own, and if they don’t have a rapid progression and they have a negative PET [positron emission tomography] scan at the time they come to attention, I’m comfortable keeping an eye on them until I start to see the hemoglobin level drop, or something else that changes my mind.

Keith Stewart, MD, ChB, MBA: That was the conservative senator from a southern state, and now a liberal from San Francisco. Nina, in San Francisco, how are you jumping on people’s therapy when they relapse?

Nina Shah, MD: I guess I’m an old soul also, and maybe I was born a little too late. I agree with Sagar in that we should use IMWG [International Myeloma Working Group]-based decision making because the clinical trials did the same thing. So if we’re going to make decisions to change therapy, then whatever the patient’s enrolled in for those trials would be, I think, the right thing to do. I agree that sometimes people will have biochemical progression, but they don’t have anything else going on. That’s a great time to talk about clinical trials and what your options are. It’s a great time to get staging done. It’s a great time to know if they’ve had clonal evolution. But I wouldn’t decide based on MRD rising because the test itself can change, depending on what year you got it. That’s another thing. I think we have more evidence to go with your standard treatment. One thing I would say about IMWG is that if there’s more light chain escape, then I would decide based on rising light chain levels. I don’t need to have the M protein at 0.5 g/dL, but if you’re worried about the light chains going up, that’s OK.

Joseph Mikhael, MD: I’m in a purple state, so I’ll be slightly different. I completely agree. I think going from MRD positivity to negativity, especially with the potential for error, isn’t the decision-making tool. The only exception, or slight difference, from what we’ve just heard is that in a high-risk patient, I’m willing to pull the trigger more quickly. I don’t want to wait for that hemoglobin level to drop and other things. Just pure biochemistry, maybe it meets IMWG criteria, as Nina said, and maybe it doesn’t quite meet that. I’m nervous about the high-risk patient relapsing aggressively and quickly. I’m more willing to jump in, whereas some of the standard-risk patients may take several months to progress.

Sagar Lonial, MD, FACP: Or years.

Keith Stewart, MD, ChB, MBA: Let me push you on that point. If you’re doing MRD testing, and you’re getting real numbers back, and twice in a row, you get 5 or 10 copies per million, then it comes back at 3000 per million, wouldn’t you consider that the time to change therapy?

Joseph Mikhael, MD: I’m not doing it frequently enough to naturally collect that. But if that were the case, especially if it’s a high-risk patient, I would expect that the light chains would change, or the M spike would change. I would be willing to jump on that, for sure. But routinely going from MRD negativity to 1 single MRD-positive is different than the sustained positive as you’ve described.

Transcript Edited for Clarity

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