What Is Measurable Residual Disease (MRD) and What’s the Impact on CLL Care?

Transcript:

Jeff Folloder: So, Dr. Wierda, earlier in the program, you mentioned the acronym MRD, minimal residual disease. David wants to know, what does that actually mean?

Dr. William Wierda:  So, this is an area that I’m extremely interested in now and doing a lot of work on. MRD means minimal residual disease or measurable residual disease, and it refers to a very low level of disease that we can test; we can detect with some of our more sensitive tests than, say, a blood count or a CAT scan.

We apply these tests to either the blood or the bone marrow, and we’re able to sort through the cells there and say, “Okay, yes, there is one CLL cell among 10,000 normal cells” or “one CLL cell among a million normal cells.” That level of detection refers to the sensitivity of the test that’s being used. So, flow cytometry is one of the tests that we use to detect minimal residual disease. The flow cytometry is more limited in its sensitivity than next-generation sequencing or a molecular test. So, the flow cytometry allows us to detect one in 10,000, one leukemia cell in 10,000 normal cells. The next-generation sequencing platform allows us to detect one leukemia cell among a million normal cells.

And you can imagine that if we’re talking about that very low level of disease, we’re talking about very effective treatments that can get rid of almost all of your CLL. And so, in the past, we’ve talked about response to treatment being measured by how big the lymph nodes are and what the blood counts are. And if we see any CLL cells under the microscope in the bone marrow, now we’re talking about remissions where we’ve gone beyond that, where we need to use these very sensitive tests to pick up very small levels of CLL.

And so, our new clinical trials are aimed at eliminating minimal residual disease. We feel that if we can get patients into an MRD-negative or a minimal residual disease-free remission, this is going to be correlated and associated with the longest remission and potentially a cure of the CLL.

Jeff Folloder:  So, that begs the question, how far away are we from MRD-directed, time-limited therapy in standard community settings around the world? How far on the horizon is this?

Dr. William Wierda:  Well, that requires us to have data, clinical trial data that will support doctors doing, practicing, and providing treatments according to how it was done on a clinical trial. Right now, there are ongoing clinical trials where patients are getting MRD-directed therapy. We’ve seen some data already where outcomes are reported with regard to MRD-directed therapy. There’s a large trial that the British did called the FLAIR trial where patients received ibrutinib plus venetoclax that was MRD-directed, and outcomes were superior for patients who became MRD-undetectable with that treatment.

So, we will see treatment options on the NCCN guidelines that are MRD-directed in the very near future, and I’m sure at this coming ASH, we’ll see new data out for clinical trials where treatment was given in an MRD-directed fashion. I think that’s where we’re going in general in the future for all of our time-limited therapies.