Cancer Conference Update: A Multimedia Review of Key Presentations from the 2016 American Society of Hematology Annual MeetingAbstract 619: Results from KEYNOTE-013 — A Phase Ib study of pembrolizumab in relapsed/refractory primary mediastinal large B-cell lymphoma
3:28 minutes.
TRANSCRIPTION:
DR FLOWERS: So immunotherapy really is nothing new to lymphomas. The place where we’ve seen the greatest activity in pembrolizumab and nivolumab is in Hodgkin lymphoma. And it only stands to reason that primary mediastinal diffuse large B-cell lymphoma would be one of the other places to look, since it holds such close histological connections and biological connections to Hodgkin lymphoma. So in this trial — this was the KEYNOTE-013 trial — they looked at patients with relapsed and refractory primary mediastinal diffuse large B-cell lymphoma where patients received pembrolizumab, but 10 mg every 2 weeks, and then as we gained more experience with the use of pembrolizumab, it was changed to the more standard approach that we use now, giving 200 mg every 3 weeks. And what was seen in this setting in a relatively small number of patients — so 18 patients who were treated on trial — that the overall response rate was 41% in this population, although the majority of those patients achieved partial responses, 35% had stable disease as their best response. I think this disease entity is one that when we look at it in the relapsed setting is one that is fraught with a number of challenges. The vast majority of these patients are cured in the front-line setting. But as we’re moving now away from radiation, we may start to see more of these patients relapsing and looking at this agent as one that can have a role in primary mediastinal diffuse large B-cell lymphoma in the future. DR LOVE: Does it basically look similar in efficacy to what you see with HL? DR FLOWERS: Maybe not quite the level of efficacy that you see in patients with Hodgkin lymphoma, but it is quite impressive for a relapsed and refractory patient population to see this. DR LOVE: And I’m trying to remember the exact biologic/genomic reason for why HL responds so well. Could you go through that? And is that also seen with mediastinal large cell? DR FLOWERS: So when you look at mediastinal large cell, that has not been teased out to the same level of detail as what was seen in Hodgkin lymphoma. So the genetic aberrations that are seen in Hodgkin lymphoma are most commonly associated with PD-L1 expression. And it’s that PD-L1 expression that we see in the Hodgkin lymphoma cells that make them very sensitive to PD-1 inhibitors in particular. DR LOVE: You mentioned the fact you don’t see that many patients who relapse. But have you encountered any patients? Would you use a PD-1 antibody in these patients outside a trial setting? DR FLOWERS: I think, because of the tolerability of these agents and because of the challenges that we face with patients with diffuse large B-cell lymphoma in general and primary mediastinal diffuse large B-cell lymphoma in specific, once patients have failed an autologous stem cell transplant, their changes of responding to any other agent are in the 10% or less range. And so I think this is an important agent to consider in that setting. |