Management of Transplant-Ineligible Multiple Myeloma - Episode 4

MRD Testing in Multiple Myeloma

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Current techniques used to assess MRD status in patients with multiple myeloma, and advice to hematologist-oncologists who are considering flow cytometry or molecular testing.

Robert Orlowski, MD, PhD: Let’s go to the next polling question. This question has to do with what an adequate treatment response for this kind of transplant-ineligible patient is.

Robert Orlowski, MD, PhD: So far we’ve got 1 vote for stringent CR [complete response]. Now we’ve got CR coming up, and VGPR [very good partial response]. Let’s give this a few more moments so other people can vote.

Larry Anderson, MD, PhD: While we’re waiting, 1 of the things to point out is you brought up the mass fix at Mayo Clinic. To call it a stringent CR if they’re on monoclonal antibodies, for a lot of these patients you might have to do mass fix or something similar to know if the band that they have is residual myeloma protein. Or is it just the Darzalex in their electrophoresis?

Robert Orlowski, MD, PhD: Larry, because you brought that up, can you explain quickly for the audience how that’s done and why it’s a nice test that, hopefully, people will use more often?

Larry Anderson, MD, PhD: For us, we send out to Mayo. They send that serum there, and they separate out all the proteins in the serum by size and charge on a mass spectrometry machine. That tells you if you have a peak of lambda light chains or capitalized chains or IgG protein, and they can go so far as to say, this is the same exact mass as the daratumumab molecule or elotuzumab molecule. They can tell you if it’s from their treatment. It’s also sensitive in picking up every minute, monoclonal spikes that may not necessarily show up on a regular electrophoresis.

Robert Orlowski, MD, PhD: Caitlin, what do you think about the results that we’re seeing? We’ve got 4 votes for CR, 3 for stringent CR, and 1 for MRD [minimal residual disease] negativity. It looks like people are ambitious. Then we’ve got a few votes for PR and VGPR as well. What are your thoughts?

Caitlin Costello, MD: Let’s just say the context is with a transplant-ineligible patient. We want to do well by them, but we don’t need to keep pummeling things either. I’d like to see a VGPR or better. Of course, the idealist in me would love to see a stringent CR, MRD negativity. But if I get to a VGPR and someone who’s frail or older can’t continue therapy or whatever it is, then that’s bad for adequacy.

Robert Orlowski, MD, PhD: Jeff, Larry, any disagreements with that?

Larry Anderson, MD, PhD: I agree.

Jeff Matous, MD: I agree as well.

Robert Orlowski, MD, PhD: Excellent. The next topic for the panel discussion was about MRD, how it’s measured, and advantages and limitations. We’ve talked about that already, but Jeff, maybe you can tell us, you mentioned that you do clonoSEQ and we’ve also talked about the MRD by flow [cytometry], which are probably the 2 most prevalent methods right now. Walk us through a little how they’re different from what their strengths and weaknesses are.

Jeff Matous, MD: The most readily available technique for obtaining MRD negativity is flow cytometry. You don’t need a baseline sample to run it. You can run it on a marrow, and it’s good for 10-4. If you’re really confident, some might say even better than that, but probably not. The problem is that not all flow is the same, and it depends on the freshness of the sample, how many cells are counted, how confident you are in your flow lab, but it’s readily available. It’s what we have. I tell my patients that if we’re negative by flow [cytometry] on a marrow after we’ve done some treatments, let’s say a transplant or something else, then that’s pretty good. A lot of the studies out there, particularly older studies, use flow cytometry as their method of MRD.

With molecular testing, as that we see with clonoSEQ next-generation sequencing, that technique is more sensitive. It’s good for 10-5 or 10-6 and very sensitive, but it requires a baseline sample to perform. You can run that baseline sample on older pathology that might be from a biopsy that was done at a different place 3 months ago. Then a fresh sample to run. It’s more daunting for the staff sometimes if you’re in a busy practice to say, “I want to run MRD in this guy by clonoSEQ, and you have to get set up to do it at your institution to run clonoSEQ as well.” I tend to do more of the molecular techniques in my younger patients, for whom I’m more aggressive. Flow [cytometry] is an excellent technique as well, but you have to be aware of the quality of your flow.

Transcript edited for clarity.