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Untreated Follicular Lymphoma and the Role of MRD Testing

Insights From: Scott Huntington, MD, MPH, MSc, Yale University; Laurie H. Sehn, MD, MPH, BC Cancer
Published: Friday, Feb 07, 2020



Transcript: 

Laurie H. Sehn, MD, MPH: This trial was a single-arm study with the combination of obinutuzumab and lenalidomide in patients with high-tumor-burden follicular lymphoma who were previously untreated. What we see from the results of this trial is that there was remarkable efficacy with an overall response rate of 98% and a CR [complete response] rate of 92%, which is really very striking in this patient population.
We learned from the RELEVANCE trial that compared head-to-head rituximab with lenalidomide against chemotherapy and rituximab that the combination of R2 [lenalidomide, rituximab] was very promising and actually highly comparable to chemotherapy in the untreated setting. Given the fact that obinutuzumab is a monoclonal antibody that’s shown greater efficacy than rituximab in follicular lymphoma, I think that this is a very logical combination to test because the assumption is that should make the previous R2 [lenalidomide, rituximab] regimen better. I think these results are highly enticing and that it is a very effective combination.

Scott Huntington, MD, MPH, MSc: Similar to other hematologic malignancies, there’s been increased enthusiasm about using MRD [minimal residual disease] testing in follicular lymphoma. And follicular lymphoma MRD testing is still a research question. We don’t have the ability of using MRD for predicting which therapy we should either intensify to or perhaps stop therapy. But it’s a really active scientific question right now. Can we interpret MRD testing? Either during therapy in these adaptive approaches or during the monitoring of patients who have received first-line therapy. Is the role of MRD testing to adapt our subsequent lines of therapy?

MRD testing in follicular lymphoma follows a quantitative PCR [pathologic complete response] approach in which we’re looking at the BCL2, a heavy chain rearrangement transcript. If 10% of follicular lymphomas won’t have that BCL2 rearrangement, we can use the same PCR technology to identify heavy chain variation. It’s PCR based, unlike a flow cytometry base, which proceeded much of our MRD testing. MRD testing for follicular lymphoma is using quantifying PCR.

Laurie H. Sehn, MD, MPH: The value of MRD testing in follicular lymphoma is it does potentially provide a real objective measure of the depth of response. Many trials are now building it in as a surrogate measure for efficacy. In terms of the GADOLIN trial, it was evaluated, and what we saw is that patients receiving the combination of obinutuzumab and bendamustine had a much higher level of MRD negativity following completion of treatment compared with patients receiving the bendamustine alone. The rate of MRD negativity was approximately 86% in patients receiving the obinutuzumab versus only about 55% in patients receiving the single-agent bendamustine.

Transcript Edited for Clarity
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Transcript: 

Laurie H. Sehn, MD, MPH: This trial was a single-arm study with the combination of obinutuzumab and lenalidomide in patients with high-tumor-burden follicular lymphoma who were previously untreated. What we see from the results of this trial is that there was remarkable efficacy with an overall response rate of 98% and a CR [complete response] rate of 92%, which is really very striking in this patient population.
We learned from the RELEVANCE trial that compared head-to-head rituximab with lenalidomide against chemotherapy and rituximab that the combination of R2 [lenalidomide, rituximab] was very promising and actually highly comparable to chemotherapy in the untreated setting. Given the fact that obinutuzumab is a monoclonal antibody that’s shown greater efficacy than rituximab in follicular lymphoma, I think that this is a very logical combination to test because the assumption is that should make the previous R2 [lenalidomide, rituximab] regimen better. I think these results are highly enticing and that it is a very effective combination.

Scott Huntington, MD, MPH, MSc: Similar to other hematologic malignancies, there’s been increased enthusiasm about using MRD [minimal residual disease] testing in follicular lymphoma. And follicular lymphoma MRD testing is still a research question. We don’t have the ability of using MRD for predicting which therapy we should either intensify to or perhaps stop therapy. But it’s a really active scientific question right now. Can we interpret MRD testing? Either during therapy in these adaptive approaches or during the monitoring of patients who have received first-line therapy. Is the role of MRD testing to adapt our subsequent lines of therapy?

MRD testing in follicular lymphoma follows a quantitative PCR [pathologic complete response] approach in which we’re looking at the BCL2, a heavy chain rearrangement transcript. If 10% of follicular lymphomas won’t have that BCL2 rearrangement, we can use the same PCR technology to identify heavy chain variation. It’s PCR based, unlike a flow cytometry base, which proceeded much of our MRD testing. MRD testing for follicular lymphoma is using quantifying PCR.

Laurie H. Sehn, MD, MPH: The value of MRD testing in follicular lymphoma is it does potentially provide a real objective measure of the depth of response. Many trials are now building it in as a surrogate measure for efficacy. In terms of the GADOLIN trial, it was evaluated, and what we saw is that patients receiving the combination of obinutuzumab and bendamustine had a much higher level of MRD negativity following completion of treatment compared with patients receiving the bendamustine alone. The rate of MRD negativity was approximately 86% in patients receiving the obinutuzumab versus only about 55% in patients receiving the single-agent bendamustine.

Transcript Edited for Clarity
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