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Standardizing MRD Testing for CLL

Panelists: William G Wierda, MD, University of Texas MD Anderson Cancer Center; Alexey V Danilov, MD, PhD, University School of Medicine in Portland, Oregon; Matthew S Davids, MD, MMSc, Dana-Farber Cancer Institute; Anthony R Mato, MD, Memorial Sloan Kettering Cancer Center; Susan M. OBrien, MD The University of California, Irvine Medical Center
Published: Thursday, Feb 07, 2019



Transcript: 

Anthony R. Mato, MD: One of the thoughts that I had when I was sitting there listening to Peter Hillmen [MB ChB], Danielle Brander [MD], and then the MURANO data was that with the venetoclax-based regimens, we’ve now sort of opened a Pandora’s box where there may be 2 camps in terms of thinking about how to use that combination—the fixed duration camp and then the little hint from Danielle Brander that treatment to depth of response is the way to go. And so I think even though there’s obviously no comparison between this giant study and this small trial that has long-term follow-up, it raises in my mind whether or not we will ultimately, as we become more sophisticated with MRD [minimal residual disease], more uniform with MRD, be able to move in a direction where we’re actually treating based on biology.
On the flip side of the coin, I was taken aback a little bit by the fact that we still don’t have a definition of what MRD is. And when I’m starting to hear about high versus low MRD and cut points that I never knew, I think we still have so much more work to do to really nail down what that is before we can ask anybody in practice to employ that to make a decision.

William G. Wierda, MD, PhD: The thing that I would add to what you’re saying in terms of the discussion around fixed duration versus treat to an endpoint, I probably expect to see more of a hybrid. So where we’re taking a treatment and we’re giving everybody a fixed duration, and then we may modify what we do for individual patients based on where they’re at at the end of that fixed duration.

Anthony R. Mato, MD: I think so.

William G. Wierda, MD, PhD: If we’re looking at MRD or we’re looking at risk features, we maybe do something for those patients who are at high risk for progression and those who are at a particular endpoint, stop treatment. We’ve done a lot of work with MRD and looking at blood versus bone marrow, and I think for a community practice, bone marrows are probably not going to be very useful. And we’ll not probably be developing trials that the endpoint is to look at MRD in bone marrow because they’re not done in the community practice. So, I think blood MRD is probably the best place to focus our efforts.

I think for this ASH [American Society of Hematology meeting], in terms of data and data particularly that we presented from The [University of Texas] MD Anderson [Cancer Center], we talked a little bit about the iFCG [ibrutinib/fludarabine/cyclophosphamide/obinutuzumab] trial. The iFCG trial was intended to increase the depth of remission, so to achieve a high undetectable MRD status for the mutated cases with the intent of perhaps curing a higher proportion of those patients. We looked with FCR [fludarabine/cyclophosphamide/rituximab] and have shown that the higher proportion of patients you can get an undetectable MRD status [for] at the end of treatment, particularly for the mutated cases, clearly has correlated with progression-free survival and the plateau of that curve.

We’ve looked by more sensitive methods for MRD, so the standard MRD testing is at 10-4, but we’ve sent samples to Adaptive [Biotechnologies] and have a 10-6 test. With FCR, the undetectable MRD state for patients with an MRD6 assay is about 15%. With iFCG, it’s like 70% for the patients that we have data for. I’m excited about that aspect and the fact that we can get 70% of the patients undetectable MRD at 10-6, and hopefully that will enhance the cure fraction for that regimen and minimize or reduce the risk for toxicities.

Before we finish up, are there any other abstracts that we didn’t touch on or any other topics that we didn’t touch on that people think were important? We covered a lot of extensive coverage of a lot of different abstracts and material. I think it’s been a great discussion. Thank you all for your contributions to this discussion.

On behalf of our panel, we thank you for joining us, and we hope you found this OncLive Peer Exchange® to be useful and informative.


Transcript Edited for Clarity

 

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Transcript: 

Anthony R. Mato, MD: One of the thoughts that I had when I was sitting there listening to Peter Hillmen [MB ChB], Danielle Brander [MD], and then the MURANO data was that with the venetoclax-based regimens, we’ve now sort of opened a Pandora’s box where there may be 2 camps in terms of thinking about how to use that combination—the fixed duration camp and then the little hint from Danielle Brander that treatment to depth of response is the way to go. And so I think even though there’s obviously no comparison between this giant study and this small trial that has long-term follow-up, it raises in my mind whether or not we will ultimately, as we become more sophisticated with MRD [minimal residual disease], more uniform with MRD, be able to move in a direction where we’re actually treating based on biology.
On the flip side of the coin, I was taken aback a little bit by the fact that we still don’t have a definition of what MRD is. And when I’m starting to hear about high versus low MRD and cut points that I never knew, I think we still have so much more work to do to really nail down what that is before we can ask anybody in practice to employ that to make a decision.

William G. Wierda, MD, PhD: The thing that I would add to what you’re saying in terms of the discussion around fixed duration versus treat to an endpoint, I probably expect to see more of a hybrid. So where we’re taking a treatment and we’re giving everybody a fixed duration, and then we may modify what we do for individual patients based on where they’re at at the end of that fixed duration.

Anthony R. Mato, MD: I think so.

William G. Wierda, MD, PhD: If we’re looking at MRD or we’re looking at risk features, we maybe do something for those patients who are at high risk for progression and those who are at a particular endpoint, stop treatment. We’ve done a lot of work with MRD and looking at blood versus bone marrow, and I think for a community practice, bone marrows are probably not going to be very useful. And we’ll not probably be developing trials that the endpoint is to look at MRD in bone marrow because they’re not done in the community practice. So, I think blood MRD is probably the best place to focus our efforts.

I think for this ASH [American Society of Hematology meeting], in terms of data and data particularly that we presented from The [University of Texas] MD Anderson [Cancer Center], we talked a little bit about the iFCG [ibrutinib/fludarabine/cyclophosphamide/obinutuzumab] trial. The iFCG trial was intended to increase the depth of remission, so to achieve a high undetectable MRD status for the mutated cases with the intent of perhaps curing a higher proportion of those patients. We looked with FCR [fludarabine/cyclophosphamide/rituximab] and have shown that the higher proportion of patients you can get an undetectable MRD status [for] at the end of treatment, particularly for the mutated cases, clearly has correlated with progression-free survival and the plateau of that curve.

We’ve looked by more sensitive methods for MRD, so the standard MRD testing is at 10-4, but we’ve sent samples to Adaptive [Biotechnologies] and have a 10-6 test. With FCR, the undetectable MRD state for patients with an MRD6 assay is about 15%. With iFCG, it’s like 70% for the patients that we have data for. I’m excited about that aspect and the fact that we can get 70% of the patients undetectable MRD at 10-6, and hopefully that will enhance the cure fraction for that regimen and minimize or reduce the risk for toxicities.

Before we finish up, are there any other abstracts that we didn’t touch on or any other topics that we didn’t touch on that people think were important? We covered a lot of extensive coverage of a lot of different abstracts and material. I think it’s been a great discussion. Thank you all for your contributions to this discussion.

On behalf of our panel, we thank you for joining us, and we hope you found this OncLive Peer Exchange® to be useful and informative.


Transcript Edited for Clarity

 
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