MRD Testing in CLL

Anthony Mato, MD, MSCE: People have many questions about MRD [minimal residual disease]. One of the questions is, what tests do I use? What compartment do I use? At what time point do I use this type of testing, or am I using it at all to make a clinical decision? MRD stands for minimal residual disease. It will have a growing importance in the future. Are you using it at all in clinical practice? If so, what tests, what compartment, and at what time point?

Alexey Danilov, MD, PhD: I’m a bit conservative in this as well, so I tend to follow the prescribed regimen. MRD still doesn’t necessarily have a lot of data in terms of how to make decisions and tailor therapy if you’re MRD positive or MRD negative. We know it has prognostic value, but because it doesn’t necessarily change what I would do. I still don’t test it in routine clinical practice.

One circumstance where I might occasionally use it after a discussion with a patient is if somebody finishes a year of venetoclax-obinutuzumab combination based on CLL14 and they get anxious and concerned that they’ll be stopping therapy. Then I discuss with them the possibility of testing MRD. At that point, because the MRD rate is 70% in that setting, it helps me reinforce the point that it’s OK to stop. However, if it’s positive, then we have a discussion on whether it’s worth it to continue for another year, knowing that we don’t have any information that continuing venetoclax for an extra year helps improve progression-free survival in the context of positive MRD at that time point. That’s 1 circumstance where I have used it outside a clinical trial. And I use flow-based MRD. I’ve occasionally used clonoSEQ assay for patients who have progressed through multiple therapies and are concerned about their subsequent therapeutic approach, but that’s also a very rare situation. For the majority of my patients, I haven’t been necessarily testing for MRD.

Anthony Mato, MD, MSCE: I agree. In clinical practice, I use it at the same decision point as you do after the completion of venetoclax-based therapy, particularly in high-risk patients. I’m using both flow and next-generation sequencing. I’m trying to get a feel for both. Although on our trials, we have pretty much given up on flow cytometry because it’s impossible to standardize across sites and switched more to the clonoSEQ assay, mostly because I’m trying to make decisions for MRD based on deeper levels of remission than just 10-4. Our stopping rules are either at 10-5 or 10-6 in the peripheral blood, and I can’t get that with flow cytometry, so I’ve walked away from it for the most part.

Alexey Danilov, MD, PhD: It’s still an evolving concept, and that’s another … 10-6 is even less than with flow cytometry, so we’d still need even more data before we make daily decisions in the clinic.

Anthony Mato, MD, MSCE: In the context of clinical trials, when we start to compare these regimens, like ibrutinib-venetoclax or venetoclax-obinutuzumab or whichever, at 10-4, they’re all going to have such high rates of MRD or undetectable residual disease. Maybe only 1 of the ways to distinguish 1 from the other, the doublets vs the triplets or whichever of the venetoclax-based therapies, might be to use the clonoSEQ, where we can nuance the proportion of patients who are at 10-5 or 10-6. We won’t get that from flow, which is another reason I’ve walked away from that a bit.

Transcript edited for clarity.