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Sequencing Strategies in Frontline CLL

Insights From: Michael Choi, MD, UC San Diego Medical Center; Matthew S. Davids, MD, Dana-Farber Cancer Institute; William Wierda, MD, PhD, MD Anderson Cancer Center
Published: Tuesday, May 01, 2018



Transcript: 

William Wierda, MD, PhD: The NCCN guidelines have changed. The NCCN guidelines get updated based on new data, and treatments get integrated into the NCCN guidelines when the data become available, whether it’s at an ASH meeting and the data have been presented or the trials that have been reported in the literature. The changes and evolution in the NCCN guidelines have recently been reflective of the trials that have reported out. RESONATE-2 had the data that supported the NCCN guidelines having ibrutinib as a category-1 first-line treatment. It’s also in there as a category 1 treatment for relapsed patients. The NCCN guidelines are updated as the trial data become available. We update them twice a year, after the ASH meeting and then in the late Spring. And as I mentioned, they’re reflective of what’s happening in terms of practice patterns and the data that are coming out.

At MD Anderson, we follow the data. If we’re treating patients off of clinical trials, then we follow the data. Our practice patterns at MD Anderson do reflect, for the most part, what the data indicate for treatment and what’s reflected in the NCCN guidelines. For example, regarding patients who have an unmutated V gene and need their first-line therapy, we’ll be more inclined to treat those patients with a BTK inhibitor–based therapy, and we will use chemoimmunotherapy, particularly FCR, for patients who have a mutated V gene.

This distinction between a mutated versus unmutated V gene and tailoring treatment with regard to that have not yet fully been incorporated into the guidelines, but I think at the next meeting that will probably happen because those data came. There was a report from MD Anderson where patients who had a plateau on their progression-free survival curve were among the patients who had a mutated V gene and got FCR. The Germans have confirmed those data independently in randomized trials. So, there are clearly plenty of data that would support that distinction and approach for the management for those patients.

Michael Choi, MD: The question regarding first-line maintenance therapy is a good one, but perhaps one that’s becoming less relevant now that drugs like ibrutinib are increasingly being used. That said, there have been some large studies, including the German CLL Group study, looking at lenalidomide as a consolidation or maintenance therapy after frontline chemoimmunotherapy. The study did show a reduction in risk of progression and improvement in responses for some patients, so I think it does show that lenalidomide is an option for patients who have residual disease after frontline chemoimmunotherapy.

However, it’s also notable that the patients who received lenalidomide in that trial were the minority. Most patients either had very little residual disease or did not have the adverse prognostic factors that would have qualified them for lenalidomide. So, I think that regimen, the continuation with lenalidomide, does not apply to all or many patients. But it is something that one can consider, perhaps for patients who have to stop chemoimmunotherapy early due to toxicity.

Transcript Edited for Clarity 
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Transcript: 

William Wierda, MD, PhD: The NCCN guidelines have changed. The NCCN guidelines get updated based on new data, and treatments get integrated into the NCCN guidelines when the data become available, whether it’s at an ASH meeting and the data have been presented or the trials that have been reported in the literature. The changes and evolution in the NCCN guidelines have recently been reflective of the trials that have reported out. RESONATE-2 had the data that supported the NCCN guidelines having ibrutinib as a category-1 first-line treatment. It’s also in there as a category 1 treatment for relapsed patients. The NCCN guidelines are updated as the trial data become available. We update them twice a year, after the ASH meeting and then in the late Spring. And as I mentioned, they’re reflective of what’s happening in terms of practice patterns and the data that are coming out.

At MD Anderson, we follow the data. If we’re treating patients off of clinical trials, then we follow the data. Our practice patterns at MD Anderson do reflect, for the most part, what the data indicate for treatment and what’s reflected in the NCCN guidelines. For example, regarding patients who have an unmutated V gene and need their first-line therapy, we’ll be more inclined to treat those patients with a BTK inhibitor–based therapy, and we will use chemoimmunotherapy, particularly FCR, for patients who have a mutated V gene.

This distinction between a mutated versus unmutated V gene and tailoring treatment with regard to that have not yet fully been incorporated into the guidelines, but I think at the next meeting that will probably happen because those data came. There was a report from MD Anderson where patients who had a plateau on their progression-free survival curve were among the patients who had a mutated V gene and got FCR. The Germans have confirmed those data independently in randomized trials. So, there are clearly plenty of data that would support that distinction and approach for the management for those patients.

Michael Choi, MD: The question regarding first-line maintenance therapy is a good one, but perhaps one that’s becoming less relevant now that drugs like ibrutinib are increasingly being used. That said, there have been some large studies, including the German CLL Group study, looking at lenalidomide as a consolidation or maintenance therapy after frontline chemoimmunotherapy. The study did show a reduction in risk of progression and improvement in responses for some patients, so I think it does show that lenalidomide is an option for patients who have residual disease after frontline chemoimmunotherapy.

However, it’s also notable that the patients who received lenalidomide in that trial were the minority. Most patients either had very little residual disease or did not have the adverse prognostic factors that would have qualified them for lenalidomide. So, I think that regimen, the continuation with lenalidomide, does not apply to all or many patients. But it is something that one can consider, perhaps for patients who have to stop chemoimmunotherapy early due to toxicity.

Transcript Edited for Clarity 
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