Noopur Raje, MD, Massachusetts General Hospital, Boston, MA, discusses areas of improvement in anti-BCMA CAR T-cell therapy in multiple myeloma, including evaluating the durability of response to CAR T-cell therapy, as well as the use of off-the-shelf allogeneic CAR-T products. This interview was recorded via an online conference call with The Video Journal of Hematological Oncology (VJHemOnc).
Transcript (edited for clarity)
Lots of improvement, obviously. You know, this was chapter one in the context of CAR T-cells in multiple myeloma. The good news is with chapter one, we were able to show, as I’ve mentioned already, high response rates and acceptable toxicity. What we haven’t shown is the durability of response. So I told you already on average we seen a progression-free-survival of about 10 and a half months...
Lots of improvement, obviously. You know, this was chapter one in the context of CAR T-cells in multiple myeloma. The good news is with chapter one, we were able to show, as I’ve mentioned already, high response rates and acceptable toxicity. What we haven’t shown is the durability of response. So I told you already on average we seen a progression-free-survival of about 10 and a half months. Certainly patients who are achieving deep responses. You’re going as far out as 20 months.
But when you use a strategy such as CAR T-cells you really want a durable, and almost sort of a flattening of the curve in terms of response duration. And that’s something we haven’t yet seen in myeloma. So there’s a lot of room for improvement and there’s already work being done in that context. So there’s different CAR T-cell products which are being studied, either pre-clinically or in early phase trials, just to address this whole issue of durability of responses.
One of them being bb21217. And what this does is exposes the CAR product to bbo7, which is a PI-3-kinase inhibitor ex vivo. So this is an in vitro experiment. And the idea here is to try and enrich the memory T-cell phenotype. And by doing so the hope is that you’re going to see a remission duration, which is even more sustained than what you’re seeing with bb2121. So those are ongoing studies and hopefully we’ll see some more data on these studies at this year’s American Society of Hematology meeting.
Along the same lines you have other approaches as well. And those other approaches include different ways of creating the CAR T-cells wherein you do not use a viral rector at all. It’s the transposon approach wherein you’re using methods, not using a viral approach. And by doing so, you’re really enriching those stem-cell-like T-cells and enriching photo memory T-cell phenotype. Again, early days with these trials and we’d have to wait and see whether this translates into a clinical benefit.
And again, BCMA is a great target, we’ve demonstrated that. But it’s not the only target. And how does one go beyond BCMA? There’s work being done, looking at dual targeting. So you’re going to go now what we’re using in the clinic right now. Our second generation CARs and the hope is to go to third generation CARs.
And most exciting to me is the whole concept of off the shelf CARs or use of allogeneic CARs. They’re already in the clinic as we speak. We saw some really nice data with lymphoma and then allo CAR T-cell product. And very similar studies are ongoing in the context of multiple myeloma and spread. So stay tuned. I do think you’re going to see a lot of exciting data come out of the CAR T-cell space going forward.