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Future Outlook of CAR T-Cell Therapy for DLBCL

Panelists: Anas Younes, MD, Memorial Sloan Kettering Cancer Center
Published: Friday, May 25, 2018



Transcript: 

Anas Younes, MD: So, there are 2 things that will happen in the future. One is how to optimize CAR T-cell therapy, and this is happening now, by looking at the world-targeting of CAR T cells. So, the trend is to target CD19 and CD22, at least for B-cell malignancies. Because we learned that at least one mechanism of resistance, or escape mechanism, is losing CD19 and tumor cells. So, the CAR T cells can’t see it any more. And the other one is to combine CAR T cells with immune checkpoint inhibitors, again to make the cells more responsive against the tumors. And I think there have been other platforms to improve on the efficacy of CAR T cells.

But CAR T cells are not the only thing that’s happening. There’s also exciting news about antibody-drug conjugates and the target CD79, which is a different protein expressed on B lymphocytes. There were randomized phase II data presented last ASH showing a really very good response rate, and this will be expanded to the frontline setting with R-CHOP–based regimens to compare standard R-CHOP versus R-CHOP minus vincristine but adding the polatuzumab, which is an ADC antibody. So, this is also happening in diffuse large B-cell lymphoma.

And also, we’re starting to see an emerging field of precision medicine; how to apply the genetic alteration data that have been generated from genome sequencing to select patients for targeted agents, not just 1 drug, 1 gene. It will be a combination of genes with a combination of drugs for selected patients and a precision medicine kind-of clinical trial.

So, yes, it’s an exciting time. I think it’s very good for patients. The field, at least in diffuse large B-cell lymphoma, has been stalled for almost 4 decades. We’ve been trying our best for 40 years by testing different agents and combination selection. Unfortunately, none of them have been successful. Now, we’re starting to see some emerging data and successful stories. CAR T-cell therapy is the first one, ADC may be the second one, and I think more precision medicine in the selection and genomics is going to be the next thing to be excited about.

Transcript Edited for Clarity 
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Transcript: 

Anas Younes, MD: So, there are 2 things that will happen in the future. One is how to optimize CAR T-cell therapy, and this is happening now, by looking at the world-targeting of CAR T cells. So, the trend is to target CD19 and CD22, at least for B-cell malignancies. Because we learned that at least one mechanism of resistance, or escape mechanism, is losing CD19 and tumor cells. So, the CAR T cells can’t see it any more. And the other one is to combine CAR T cells with immune checkpoint inhibitors, again to make the cells more responsive against the tumors. And I think there have been other platforms to improve on the efficacy of CAR T cells.

But CAR T cells are not the only thing that’s happening. There’s also exciting news about antibody-drug conjugates and the target CD79, which is a different protein expressed on B lymphocytes. There were randomized phase II data presented last ASH showing a really very good response rate, and this will be expanded to the frontline setting with R-CHOP–based regimens to compare standard R-CHOP versus R-CHOP minus vincristine but adding the polatuzumab, which is an ADC antibody. So, this is also happening in diffuse large B-cell lymphoma.

And also, we’re starting to see an emerging field of precision medicine; how to apply the genetic alteration data that have been generated from genome sequencing to select patients for targeted agents, not just 1 drug, 1 gene. It will be a combination of genes with a combination of drugs for selected patients and a precision medicine kind-of clinical trial.

So, yes, it’s an exciting time. I think it’s very good for patients. The field, at least in diffuse large B-cell lymphoma, has been stalled for almost 4 decades. We’ve been trying our best for 40 years by testing different agents and combination selection. Unfortunately, none of them have been successful. Now, we’re starting to see some emerging data and successful stories. CAR T-cell therapy is the first one, ADC may be the second one, and I think more precision medicine in the selection and genomics is going to be the next thing to be excited about.

Transcript Edited for Clarity 
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