EHA 2016
PD-1 enhances elotuzumab efficacy
Dr Natalie Bezman - Bristol-Meyers Squibb, Princeton, USA
We just presented pre-clinical data showing the efficacy of two antibodies, anti-PD1 and elotuzumab in mouse tumour models. The rationale for the study is that elotuzumab is an approved agent for treatment of multiple myeloma and it is a tumour-targeting antibody and it works by using cells of the innate immune system. It kills myeloma cells via a mechanism called ADCC which stands for antibody dependent cellular cytotoxicity. The second agent that we were studying was anti-PD1 and PD1 is a checkpoint receptor, it’s an inhibitor receptor that’s been characterised to regulate adaptive immune cell response to the tumour and a lot of data, recent data from both pre-clinical studies as well as more recently clinical trials, have showed the efficacy of anti-PD1 blocking antibody in multiple solid malignancies and more recently in hematologic malignancy in Hodgkin lymphoma. So the rationale was that if we combine two agents that work on two different arms of the immune system, the innate immune arm and an adaptive immune arm, we’ll be able to elicit a better anti-tumour response. This is what we observed in our mouse models when we combined elotuzumab with anti-PD1 blocking antibody we saw an enhanced anti-tumour response, tumours regressed, there was increased mouse survival and the more mechanistic studies have shown that this is due to infiltration and increased activation of both cells of the innate and adaptive immune system. So we’re taking two arms and increasing them simultaneously. So this pre-clinical data from mouse studies really provided us with the rationale to continue and test this combination of elotuzumab and anti-PD1 in patients with multiple myeloma and that’s indeed the trial that has just been initiated.
Just speaking about some of the mechanisms there, could you talk more about the elotuzumab binding pathways?
Yes, it binds to a receptor that’s overexpressed with myeloma cells and that’s one of the mechanisms by which it kills myeloma cells. Also SLAMF7, which is its target, is also expressed on NK cells themselves so it activates these cells simultaneously.
You’ve addressed the outcomes and the ongoing future trials, is that still recruiting for patient cohort?
Yes, it’s just begun, I believe, in March a recruitment. So it’s just beginning. It’s an incredibly exciting time and there is definitely pre-clinical data suggesting for the role of PD-1 pathway in multiple myeloma so I guess time will tell how it works in patients but data from solid tumours particularly and Hodgkin lymphoma recently have definitely shown that it is capable of improving an immune response to tumours so hopefully will do the same in the context of multiple myeloma.
