Hematologic Oncology Update, Issue 3, 2016 (Video Program) - Video 25Biologic rationale for combining daratumumab with immunomodulatory drugs or immune checkpoint inhibitors
1:59 minutes.
TRANSCRIPTION:
DR LONIAL: I think daratumumab does a couple of things. I think that interacting with CD38 by itself actually can kill myeloma cells. And so I think it does have the ADCP and ADCC and all those other immune-mediated effects that it has. But I think it also has direct antitumor effects. I think the second thing that we’ve seen that’s really very interesting — and it’s soft data, it’s not hard data — is the fact that it may rewire immune function a little bit. It does eliminate myeloid dendritic suppressor cells. It probably knocks out T regs as well. And that may make it a perfect partner for something like a checkpoint inhibitor to come in, because you’ve eliminated part of the brakes, and then the PD-1 inhibitor comes in and does the rest. DR LOVE: It kind of seems through, I guess, indirect comparisons at this point that maybe the IMiD combinations with daratumumab might be more effective than proteasome inhibitors? DR LONIAL: I’ve believed for a long time that the interaction between and IMiD and an antibody is probably one of the most powerful, potent things we have. And I’ve got a slide — and I think I may have showed it at the meeting at ASCO together, we did together — where you have 1 drug, 1 target, 2 different cells and 2 different effects. And that is, the effects of an IMiD on a myeloma cell are to ultimately kill that myeloma cell. But the effect of that same drug on a T cell or an NK cell is to actually activate that immune cell. And what really strikes that home to me is, we’ve treated a number of patients that are either resistant to pom or dara or both with both drugs together. And we’ve seen at least 30% of patients respond. So I think the idea, as you and I have talked about in the past, the solid tumor, the patient’s resistant to a drug, we’re going to throw it out. That is not the case with an IMiD/antibody combination, where you can resensitize, because of the immune effects. |