Cancer Conference Update: A Multimedia Review of Key Presentations from the 2016 American Society of Hematology Annual MeetingAbstract 104: Brentuximab vedotin with R-CHP as front-line therapy in high-intermediate/high-risk diffuse large B-cell lymphoma (DLBCL)
4:46 minutes.
TRANSCRIPTION:
DR FLOWERS: So B-vedotin is an agent, as you’re very familiar with, that’s been broadly applied in Hodgkin lymphoma, has activity in T-cell lymphoma, but there are a number of other malignancies that are CD30-positive where this can be applied. And, in fact, if you look at the numbers of patients that are CD30-positive, there are many more diffuse large B-cell lymphoma patients who are CD30-positive than there are Hodgkin and T-cell lymphoma patients probably put together. And so I think this was an approach to try and address that opportunity for patients with diffuse large B-cell lymphoma, combining B-vedotin with chemotherapy in the up-front setting, particularly for patients with high-risk features, where we know that high-risk diffuse large B-cell lymphoma patients do not fare nearly as well with R-CHOP therapy as either the standard-risk or the low-risk patient populations. And so in this combination, B-vedotin given at its typical dose of 1.8 mg/kg was combined both in looking at R-CHOP and then eventually with R-CHP, so dropping the vincristine from the chemotherapy regimen. When you look at this regimen in particularly the group of patients who got the R-CHP regimen, this does appear to be a tolerable regimen with limited neurotoxicity. The most frequent adverse events seen were alopecia, nausea and fatigue, which, predominantly, are likely due to the chemotherapy component of it. Peripheral neuropathy and constipation, which may be another form of neuropathy in some instances of patients, was seen in about half of patients. So this is something that you need to consider as an additional toxicity that may be a result of the B-vedotin. But, by and large, this was a reasonably well-tolerated compound. When you look at the progression-free survival, that was seen in this particular patient population for those who had CD30 expression. That was about 79% versus 58% for those who were CD30-negative. So we do see responses in patients that are CD30-positive and CD30-negative, as has been seen in other trials of B-vedotin as a single agent. I think what becomes a little bit more confusing here is to what extent B-vedotin is adding to the approach in those who are CD30-negative. But these results are meaningful enough that I think that this is an opportunity for selected patients to move this regimen forward without vincristine added as part of the chemotherapy regimen. But this needs to be compared in prospective trials to R-CHOP. DR LOVE: So are Phase III trials underway now to do this? DR FLOWERS: I know that Phase III trials have been planned looking at the combination of B-vedotin plus R-CHP versus R-CHOP. And I think we will need to see, way down the line, where this fits into play. And particularly given some of the negative trials, I think we need a number of Phase III trials moving forward to ultimately find an opportunity for improving outcomes, particularly for high-risk patients with diffuse large B-cell lymphoma. DR LOVE: So right now in your practice, how do you integrate CD30 testing into large cell lymphoma? And are you using B-vedotin, and in what situations? DR FLOWERS: Most commonly we will look at CD30 testing in patients with diffuse large B-cell lymphoma in the relapsed setting for those patients who are referred for transplant as a potential opportunity for using B-vedotin down the line, if those patients relapse after transplant. CD30 is part of our normal algorithm for lymphomas in our setting for all patients. And so we do get CD30 testing in the up-front diffuse large B-cell setting, but not something we commonly utilize for making therapeutic decisions at this point. DR LOVE: Have you seen any useful clinical responses to B-vedotin in large cell lymphoma? DR FLOWERS: So there are anecdotal responses to patients in the relapsed setting, particularly patients who have failed autologous stem cell transplant, both on trial and in our own practice for patients who have been treated off trial. |