Bispecific Antibodies | Joshua Richter, MD | ASH 2022

Hi, my name is Dr. Joshua Richter. I'm an associate professor of medicine at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, and the director of myeloma at the Blavatnik Family Chelsea Medical Center at Mount Sinai. I'm here at ASH 2022 and there's a lot of amazing data that's being presented and I've been lucky enough to be part of some of it. Some of the most exciting data this year at ASH has been in the realm of bispecific antibodies and there's two abstracts in particular involving one of the bispecifics, savastimab, that are particularly intriguing and may inform a more optimal way of using almost all of the bispecifics. Savastimab is an FCRH5 CD3 bispecific, so it's got two arms. One arm grabs onto the cancer cell, the other arm grabs onto your healthy T cell and has the T cell activated to fight the cancer cell. Now in the realm of bispecific antibodies and in fact all therapies in the relapsed refractory world of myeloma, the general approach is to continue treatment until progression or intolerability. But savastimab has done something a bit different. And here the patients receive a fixed duration of therapy for 17 cycles, approximately one year and then they stop. So for the first time in the relapsed refractory world we're trying to evaluate what happens when we stop all of our therapy in the relapsed refractory realm and just monitor. And what we've allowed on the protocol is that patients can actually be re-treated after they progress if they've been off the therapy for a while. But what's truly amazing is we have a number of patients who have completed the 17 cycles and are now six months without any therapy and still in remission and we even have some more than 12 months that remain in wonderful remissions without ongoing therapy. So we recognize that continual bispecifics can exhaust T cells and potentially to other infections so the kind of understanding that maybe there's a more fixed duration approach is extremely exciting. And I've been really happy to be part of that study. In one of the sub-cohorts that's actually been conducted outside the U.S., we've actually looked at using savastimab but pre-medicating patients with tocilizumab. Savastimab is the anti-IL6 drug that's used to treat the signs and symptoms of CRS. But some protocols in the CAR-T and the bispecific world have said, well, what if we give it prophylactically? Can we mitigate that CRS without affecting efficacy? And what they found in this sub-cohort study is that patients who receive prophylactic tocilizumab had a reduction in CRS rates from over 90% to a rate in about the 30-35% range which is absolutely amazing. And so far there's been no adverse impact on outcomes. So I really think this is leading us in the future to start considering prophylactic tocilizumab for many of our bispecifics and at the same time giving them for fixed duration therapy so that we don't exhaust T cells and we don't lead to any more adverse outcomes with things like infections.