What’s Vital to Understand About MRD Status in CLL?

Our recent CLL Global Research Foundation virtual town hall featured CLL Global President, Dr. William Wierda, and Dr. Patrick Reville, Assistant Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. CLL patient advocate Jeff Folloder moderated the event. Watch the full webinar.

Transcript

Jeff Folloder:

Dr. Wierda, you mentioned MRD status, or MRD-negative status earlier. Britt wants to know what she can expect from the immune system after MRD-negative status has been achieved.

So, one, again, what is MRD status, and two, can we hope that our immune system actually gets jump started?

Dr. William Wierda:

So, MRD stands for minimal residual disease, or measurable residual disease. It refers to testing that we do either in the blood or in the bone marrow in individuals who have normal-appearing blood, normal blood counts, normal-appearing blood cells under the microscope, normal-appearing bone marrow under the microscope, but may potentially have some low level of CLL still there that we can’t identify on those rather crude tests that we do, blood counts and microscopic examination of the blood or the bone marrow.

So, MRD sort of refers to a state of very low level of disease that’s detectable, but you have to use special, very sensitive tests to detect it.

We do know that if you can get a patient in remission and to a level where you can’t even detect that minimal residual disease any longer, that’s referred to as undetectable residual disease or undetectable measurable residual disease, and undetectable MRD. If you get a patient in a deep remission where you can’t detect any MRD, that is the best quality of remission that we have currently, meaning the deepest remission.

The importance of that is that the deeper the remission, the longer – the deeper the remission or the deeper the response, the longer the remission is expected either on or off therapy. So, if we have a patient who has still residual disease detectable at the end of their treatment, at the end of a year, for example, of ibrutinib plus venetoclax.

If they’re detectable, they’re going to have a shorter remission than a patient who is undetectable who’s had that same treatment. And the question is a complicated question in terms of what happens to the immune system in patients who are undetectable. We think there’s some improvement. We do know that the T-cell counts will improve. We have not seen full recovery of patients’ immune systems, even if they become MRD undetectable.

We don’t know why that is. Maybe it’s because it takes longer than the period of time that we’ve had to observe patients after ibrutinib venetoclax who are becoming MRD undetectable. Maybe it just doesn’t restore to the normal function, and for some reason the CLL has disrupted things so much that they don’t recover their immune function. And as Patrick said earlier, that’s an area that we’re very actively interested in and investigating in our patient population.

What are the immune dysfunction characteristics before they get treatment? Do they restore their immune function when we get rid of all the detectable leukemia? And if they don’t, what are some strategies that we can use to accelerate or improve that immune restoration?

That’s an area that in medicine, there’s not a lot of data that’s been generated, there’s no other diseases that we can use, so we’re sort of on the forefront of clinical research and investigation in that area. And that is really a big unmet need for our patient population because of the risk for infection and other cancers.