ASH 2021 | MRD monitoring in CLL
Robin Foà, MD, Sapienza University of Rome, Rome, Italy, discusses the use of measurable residual disease (MRD) monitoring in chronic lymphocytic leukemia (CLL), comparing it to its role in indolent non-Hodgkin lymphoma (NHL). In recent years, new treatment modalities have enabled a large number of patients with CLL to achieve MRD negativity. Despite its common use in clinical trials, MRD negativity is currently not used in daily clinical practice, nor as a treatment endpoint in CLL in contrast to other hematological malignancies. With a majority of patients with CLL initiating therapy at an older age, MRD monitoring has not yet been implemented in clinical practice. Prof. Foà additionally discusses the relevance of chemoimmunotherapy in the context of new effective therapies for CLL. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.
Transcript (edited for clarity)
Even in CLL, despite the enormous amount of work, that in more recent years, I mentioned in indolent lymphoma, we have data that go back 25 years. CLL, it’s much more recent because with a combination now that can be used with CLL, you can obtain, in many patient settings, MRD negativity. But having said this, even in CLL, it’s not in a daily clinical practice to monitor minimal residual disease...
Even in CLL, despite the enormous amount of work, that in more recent years, I mentioned in indolent lymphoma, we have data that go back 25 years. CLL, it’s much more recent because with a combination now that can be used with CLL, you can obtain, in many patient settings, MRD negativity. But having said this, even in CLL, it’s not in a daily clinical practice to monitor minimal residual disease. In other words, in a daily clinical practice, we always say that today, MRD negativity should not be an endpoint of treatment. Now, why am I saying this? Because, it’s very different if you’re treating an acute lymphoblastic leukemia, for instance. Where, if you want to cure the disease, you have to “eradicate” as much as possible disease. Eliminate and hopefully eradicate disease.
So, the endpoint of treatment in acute lymphoblastic leukemia is for instance, MRD negativity, molecular. And then we have to obtain that, because if a patient remains MRD positive, the likelihood that he or she will relapse is high. So, this is a big difference with, I was talking before, of indolent lymphoma, now CLL. These are conditions where the outcome is much better, obviously, and we often do not need to eradicate the disease. And CLL, maybe there’s some exceptions with the cases that have a very poor prognostic profile, namely, cell TP deletion or P53 mutation. But these are minority of patients. So, even in CLL, which is a typical paradigm where MRD is used very frequently or in all clinical trials, it’s not, as an indolent lymphoma, it is not today in a clinical practice.
Again, this may change, but today this is the case. So, one thing is to put a patient in a clinical trial and therefore MRD is monitored. Different scenario is, in a daily clinical practice, you don’t need to actually monitor minimal residual disease. So that, I think it will put the parallel between CLL and indolent lymphoma. And I think we should recognize that there’s obviously a difference in outcome between these conditions, and for instance, acute leukemia.
And the final point, I think we should also underline in CLL, that the median age of presentation CLL is about 70 or 72. Many patients we do not need to treat for a number of years, so the median age at the time of treatment, the first treatment, is about 75, 76. So, I’m not saying these individuals are old, I’m saying that they are mature, put it that way. So, we don’t need to be very aggressive. So, that’s why MRD is not yet part of the treatment. Although, as I said, for indolent lymphoma, I repeated for CLL, this is certainly included in all the clinical trials.
And my final point in CLL, and I’ll close, just to remind ourselves that even in the era of the new drugs, the new combinations, which is certainly very effective, I would like to recall whoever is listening to us that, you can obtain a state of MRD negativity with old, conventional chemoimmunotherapy. So, that’s something to recall, that the old forms of treatment have not disappeared. And so, we have to keep this in mind. It’s a minority of patients, but minority of patients, with a good biological profile, can obtain a state of MRD negativity, even with FCR. So, this is something that you keep in mind. And final point comes to my mind, let’s keep this in mind. Particularly as the world is very vast and obviously there are financial considerations that have to be considered. All the new drugs are not always available. So, the old drugs are still valuable, maybe for minority of patients, but they are still something that we should consider.
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