Can CAR T-cell therapy response deepen over time? Dr. Ciara Freeman, a myeloma specialist from Moffitt Cancer Center, discusses how the effectiveness of treatment is monitored over time, including the role of minimal residual disease (MRD) testing in follow-up care.
Dr. Ciara Freeman is an Associate Member and Clinical Research Medical Director in the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center in Tampa, FL. Learn more about Dr. Freeman.
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Transcript
Laura Beth Ezzell:
Dr. Freeman, can treatment response improve over time, or is it immediate?
Dr. Ciara Freeman:
So, treatment responses, certainly in terms of the way that we measure them, especially in myeloma, can absolutely deepen over time. So, what we see, for example, in patients who have what’s called this monoclonal protein, it’s quite a big and heavy molecule.
And sometimes, what we’ll see – and if we do, for example, lab work early – they’ll still have this measurable protein that has been made by their cancer cells, even though all the cancer cells the next time we look in the marrow are completely obliterated and gone, and they’ve got no evidence of any disease anywhere. And what happens is sometimes that M protein takes a long time to be broken down by the body. So, when we map it out over time, it’s just gradually decreasing, kind of decaying over time, if you will. And so, that’s where we’ll see those deepening responses over time.
Laura Beth Ezzell:
Yeah. And related to follow-up care with your healthcare team, how often do patients undergo follow-up scans and testing?
Dr. Ciara Freeman:
So, patients will have regular blood tests in the early days, especially when we’re trying to monitor how they’ve recovered in terms of their counts, and making sure that they don’t need any support for transfusions, et cetera. And then, we’ve got quite a standardized approach to when we’ll do bone marrows and imaging and reassessments, and we try to not overdo those. It’s important for us to make sure that we’ve got an early indication of how patients are doing, but also these are procedures that patients don’t want to have, if they don’t need them.
So, we’ve got quite a strict protocol, where we’ll do them at the early time point. The earliest time point that we’ll often do those kinds of testing, marrow and PET scan, is at 90 days. So, about three months after the cells. And then, we often won’t do them again until a year out, outside of clinical trials. So, in between time, they’ll have regular lab work done, keeping an eye on their counts and keeping an eye on their myeloma labs.
Sometimes we’ll do a little bit more imaging, if patients have the kind of myeloma where it mostly forms lumps in the body, rather than is followed by the blood. And so, ongoing assessment is definitely tailored to the patient, and we keep a close eye on them, depending on what makes sense for their body and their disease.
Laura Beth Ezzell:
And can you explain what MRD negativity means?
Dr. Ciara Freeman:
Absolutely. So, it’s a certainly a very important topic in patients with multiple myeloma. MRD stands for minimal residual disease.
Some people say measurable residual disease. There are a number of ways that you can do it. You can do it with a super fancy flow-based assay, or you can do it with a genetic assay called next-generation sequencing. A common company that’s used by a lot of providers is called Adaptive, and they do something called clonoSEQ.
How I describe it to patients is they basically get a fingerprint of your original disease, and as long as they can get that original fingerprint, then they can use that fingerprint to look at a high level of sensitivity in every bone marrow that you have sent off after that time point. So, with the next-generation sequencing, you do need that index fingerprint. If you don’t get that index fingerprint, you can’t follow it over time.
Once you get it, you can actually look for evidence of multiple myeloma at a sensitivity of one in a million cells. So, you can take out four or five million cells out of the bone marrow, send them off to this company, and then find whether there’s zero, at a sensitivity of one in a million.
And that’s the golden number that all patients want to get to, where we looked as hard as we could, and even one in a million we can’t find. It’s certainly one of the strongest predictors of long-term disease control. It’s certainly part of the bigger picture, but not the whole story.
So, we need to also make sure that we’re keeping an eye on patients with imaging, as well, because sometimes their marrow is very well cleared out with CAR T-cell therapy, but sometimes we’ll see what’s called extramedullary disease. And that’s where the disease relapses outside of the marrow, and we only see that on imaging. And sometimes, we miss out if we only look at the marrow.