Role of Minimal Residual Disease in the Management of CLL: How Do We Use it and When?

At the 2022 Lymphoma, Leukemia & Myeloma Congress in New York, Othman Al-Sawaf, MD, University Hospital of Cologne, Cologne, Germany, provided insights into the role of minimal residual disease (MRD) in the context of managing patients with chronic lymphocytic leukemia (CLL).

Transcript:

My name's Othman Al-Sawaf and I'm a hematologist and medical oncologist from the University Hospital of Cologne and the German CLL Study Group in Germany. Here at this 2022 Leukemia, Lymphoma and Myeloma [Congress] in New York City, I had the chance to speak about the role of minimal residual disease—where to use it and when to use it in the context of the management of CLL.

I first started off by showing that response assessment is something that is very commonly used in medical oncology, and in hematology, because it allows us to identify whether a patient has or hasn't responded sufficiently to any sort of treatment. And minimal residual disease has certain advantages over normal response assessment that's based on clinical features or on imaging, in that it is much more sensitive. It also allows us to quantify residual disease levels in a very accurate way.

I summarized the 3 key methods of flow optometry, PCR, and next-generation-sequencing, and highlighted that with these quantitative measures from peripheral blood, we can gain very valuable prognostic information that is in fact much more prognostically meaningful than residual lymph node size, or any other conventional clinical response feature. I also highlighted that, beyond the prognostic information that the end of treatment MRD status can deliver, the key question is whether we can act upon these MRD values. Can we, for instance, intensify treatment or should we in fact modify any sort of treatment if we see that the patient still has detectable MRD or not?

So far, this hasn't been explored in a prospective randomized way. I summarized various approaches that have been suggested and proposed by different study groups where they demonstrated in phase 2 studies that in principle it is possible to modify a treatment based on an end-of-treatment MRD status by, for instance, extending the treatment duration or intensifying the treatment, adding new compounds to improve efficacy.

I demonstrate that there is lack of data showing that this in any way has an advantage for patient, compared to our current approaches of fixed duration treatment or even continuous monotherapy. So, there is certainly still a need to explore this MRD-guided approach further and to understand whether we can derive any patient relevant benefit from MRD beyond prognostication.

At the end, I also summarized the associations that have been observed so far between MRD growth and different genomic aberrations and high-risk features. I showed that several studies have demonstrated and suggested that if you have high-risk disease, you are more likely to lose your MRD response earlier than a patient who doesn't have high-risk features. This suggests that beyond the single assessment of MRD, we'll probably at some point need also to take into account how likely it is that a patient based on high-risk features might lose the MRD response at some point. This makes things even more complicated.

We noticed also, in the discussions afterwards, that there is clearly a need to standardize the way in which we integrate the MRD assessment into our clinical management. I think there's still a lot to do and we saw at this meeting that there are still a lot of open questions that we in the community need to address.

Source:

Al-Sawaf, O. MRD, Why to Use It? How to Use It? Presented at Lymphoma, Leukemia & Myeloma Congress; October 18-22, 2022. New York, NY.