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The Impact of Brentuximab Vedotin as PTCL Treatment

Insights From: Stephen M. Ansell, MD, PhD, The Mayo Clinic
Published: Monday, Jan 28, 2019



Transcript: 

Stephen Ansell, MD, PhD:
Yeah. So I would say that the recently presented and published ECHELON-2 clinical trial has really been a game-changer for treatment of CD30-positive peripheral T-cell lymphoma [PTCL], both the anaplastic large cell lymphoma and CD30-positive PTCL, not otherwise specified. And the reason for that is this was a comparison of the standard CHOP [cyclophosphamide, doxorubicin, vincristine (Oncovin), and prednisone] chemotherapy, which, as we mentioned earlier, has been very modestly successful. And long-term outcomes are probably only about 30% with CHOP chemotherapy. So that was the standard arm. The experimental arm was to add brentuximab vedotin, a CD30-directed antibody–drug conjugate, to CHOP chemotherapy. But because of neuropathy that can develop with brentuximab vedotin, vincristine, which is one of the combinations of CHOP chemotherapy, was omitted.

And so that combination compared to CHOP chemotherapy showed the new combination to be much more successful, as far as a better progression-free survival, by about 10%. And I think the thing that is the most astounding is a better overall survival, meaning that patients lived longer when treated with the experimental treatment. So I think that has totally shifted the field in that the standard of care now for patients who have CD30-positive peripheral T-cell lymphoma is the addition of brentuximab vedotin to the CHOP backbone.

And I think, as we mentioned earlier, the challenge has been that that’s been kind of a less-than-optimal standard. But it was the standard purely by default, meaning that there really weren’t other regimens that were better than CHOP chemotherapy until now. So the addition of brentuximab vedotin in the CD30-positive patients has clearly made a significant difference for outcome and with all the important milestones that people care about. I think the other thing that for me was really interesting about the study—and, again, compliments to the folks who actually did the trial—is they blinded the study entirely as to who got brentuximab vedotin and who did not.

And I think the thing that to me was quite surprising: People would have expected potentially more neutropenia. People might have expected more peripheral neuropathy, but that really wasn’t very clearly any worse than with CHOP chemotherapy. So I think the good news from this trial is a more successful, more effective therapy on the one hand that doesn’t come with a particularly increased toxicity price. So, actually, all around a very promising result that I think has changed the field.

So bottom line is, everything takes time to kind of move from relapsed/refractory patients all the way up to frontline. So initial studies with brentuximab vedotin were done in relapsed and refractory patients who had failed a lot of other treatments. And in those circumstances, particularly in the anaplastic large cell lymphoma patients, there was a very high response rate that appeared very durable just as single-agent brentuximab vedotin. So that made: (1) CD30 a very valid target and (2) the use of brentuximab vedotin a very appropriate therapy to target CD30. That then moved forward now into the combination in frontline. So all told, that whole process has taken probably around 10 years.

Transcript Edited for Clarity
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Transcript: 

Stephen Ansell, MD, PhD:
Yeah. So I would say that the recently presented and published ECHELON-2 clinical trial has really been a game-changer for treatment of CD30-positive peripheral T-cell lymphoma [PTCL], both the anaplastic large cell lymphoma and CD30-positive PTCL, not otherwise specified. And the reason for that is this was a comparison of the standard CHOP [cyclophosphamide, doxorubicin, vincristine (Oncovin), and prednisone] chemotherapy, which, as we mentioned earlier, has been very modestly successful. And long-term outcomes are probably only about 30% with CHOP chemotherapy. So that was the standard arm. The experimental arm was to add brentuximab vedotin, a CD30-directed antibody–drug conjugate, to CHOP chemotherapy. But because of neuropathy that can develop with brentuximab vedotin, vincristine, which is one of the combinations of CHOP chemotherapy, was omitted.

And so that combination compared to CHOP chemotherapy showed the new combination to be much more successful, as far as a better progression-free survival, by about 10%. And I think the thing that is the most astounding is a better overall survival, meaning that patients lived longer when treated with the experimental treatment. So I think that has totally shifted the field in that the standard of care now for patients who have CD30-positive peripheral T-cell lymphoma is the addition of brentuximab vedotin to the CHOP backbone.

And I think, as we mentioned earlier, the challenge has been that that’s been kind of a less-than-optimal standard. But it was the standard purely by default, meaning that there really weren’t other regimens that were better than CHOP chemotherapy until now. So the addition of brentuximab vedotin in the CD30-positive patients has clearly made a significant difference for outcome and with all the important milestones that people care about. I think the other thing that for me was really interesting about the study—and, again, compliments to the folks who actually did the trial—is they blinded the study entirely as to who got brentuximab vedotin and who did not.

And I think the thing that to me was quite surprising: People would have expected potentially more neutropenia. People might have expected more peripheral neuropathy, but that really wasn’t very clearly any worse than with CHOP chemotherapy. So I think the good news from this trial is a more successful, more effective therapy on the one hand that doesn’t come with a particularly increased toxicity price. So, actually, all around a very promising result that I think has changed the field.

So bottom line is, everything takes time to kind of move from relapsed/refractory patients all the way up to frontline. So initial studies with brentuximab vedotin were done in relapsed and refractory patients who had failed a lot of other treatments. And in those circumstances, particularly in the anaplastic large cell lymphoma patients, there was a very high response rate that appeared very durable just as single-agent brentuximab vedotin. So that made: (1) CD30 a very valid target and (2) the use of brentuximab vedotin a very appropriate therapy to target CD30. That then moved forward now into the combination in frontline. So all told, that whole process has taken probably around 10 years.

Transcript Edited for Clarity
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