MRD Testing for CLL


Nicole Lamanna, MD: This obviously touches a little upon MRD [minimal residual disease], which we can discuss a little now. The concept of minimal residual disease with venetoclax-based therapies, and we’ll get to doublets and triplets in a minute. In the current setting, how do you all feel? Obviously, there’s a difference among clinical trials. In terms of current clinical practice, are any of you actively using MRD to guide your decisions not on a clinical trial?

Jan Burger, MD, PhD: The most effective agents we’ve been talking about, the BTK inhibitors, almost never induce MRD-negative remission. There was not so much interest in studying MRD as part of treatment for a few years. Now with the combinations, it’s getting some revival. The discussion comes from chemoimmunotherapy when MRD negativity was predicting for long-term survival with new agents and especially with the BTK inhibitors it doesn’t. Also, depth of remission doesn’t correlate, at least from data we have with duration of remission.

Nicole Lamanna, MD: Yet some of those people do well long term, regardless.

Jan Burger, MD, PhD: With the combination treatments, it’s a research topic outside clinical trials. In patients who are on venetoclax, it seems to correlate with duration of remission. In venetoclax-treated patients, it’s probably more important than in BTK inhibitor—treated patients.

Javier A. Pinilla-Ibarz, MD, PhD: I agree, and I think the question is how we really implement or incorporate this MRD without true guidelines for bringing any quality information besides the research question that we try to do. We’re just really talking about that. Do we stop after 1 year? Do we stop after each year? Well, what are we doing to make this decision? We do MRD. I think we still can discuss that it’s not really standard of care. We cannot really recommend doing it, at least in the community, when there are no other prognostic factors that are more important. I think we are doing more and more in our daily basis as a treatment decision, as we say, should we stop this patient or should we continue?

The incorporation of the new technologies maybe will allow us to follow those patients in a better or more efficacious way. It may be something that in the future we’re going to incorporate more with the data of the clinical trial but also with our standard practice. These are questions that patients ask all the time: should I stop this drug or not? However, although I completely agree with that, this is not really related with that single-agent BTK, but rather with combination. Until now, most of these combinations include a BCL2 inhibitor, venetoclax. We are talking about the CAPTIVATE trial, but we can discuss even the CLL14 trial. Both include this BCL2 inhibitor. Ultimately, is there 1 that really has a profound impact in the bone marrow and produces these very deep MRD negativities?

Nicole Lamanna, MD: Not quite ready for prime time. Need longer follow-up.

Farrukh Awan, MD: These are excellent points about the utility of MRD, but the truth of the matter is that that’s a test available in very few sites in this country in academic centers, outside a few places.

Javier A. Pinilla-Ibarz, MD, PhD: I agree with that.

Farrukh Awan, MD: No. 1, we do not have routine access to that test. Second, we should clarify for our listeners and viewers who don’t use the MRD assessment on a daily basis and don’t have to address these issues on a daily basis when they’re taking care of patients with CLL [chronic lymphocytic leukemia] as we do; this is not your regular flow.

Javier A. Pinilla-Ibarz, MD, PhD: No.

Farrukh Awan, MD: You must request a specific MRD assay if you want to get that information. The other thing we should all clarify, which is common knowledge for us but may not be for our viewers, is that there is no standardized MRD testing in this. And I think that is the whole argument. That group is doing a good job and doing it in the European centers and then hopefully somewhat here. We still need a standardized test that is freely available for a lot of our patients. We’re just not doing it. We’re not using MRD to make our decisions in the community on a day-to-day basis. Second, we don’t even know right now which 1 is necessarily the best assay to use. We understand the deeper it is, the better the outcomes would be. Should I use PCRs patient care reports for all my patients? Do I use flow for all my patients? For somebody who doesn’t only see or take care of CLL patients, these are difficult questions to incorporate in their practice. At this point, if I’m not an academic CLL specialist, it would be safe to say that this is still a question that needs to be addressed in systematic clinical trials. While we do incorporate this in our decision making, in certain academic centers, I don’t think it’s a done deal yet. There are still a lot of questions to be addressed.

Transcript Edited for Clarity

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