VIDEO: Challenges in DLBCL combination therapy research

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CAR T, as I was just saying, are fantastic, but because they're a bit labor intensive and complex, it has been harder to do more combination trials with them. By contrast, the bispecific antibodies almost came out of the gate with combination trials. After treating 150 patients in monotherapy and seeing the efficacy, we see that they are non-toxic in so many of the ways that chemo is toxic. You have side effects with bispecific antibodies, we shouldn't push that under the rug. The main side effects are this thing called cytokine release syndrome and maybe neurotoxicity as well. The thing is, most of those side effects happen entirely within the first few weeks of therapy, and after that, the side effects are much lesser.

There's still some, some neutropenia and other side effects, but overall, that safety profile combines very well with chemo, not tough on the nerves, not usually tough on most of the blood cells. So the simplest thing, just chemo plus bispecifics, awesomely effective, as we chatted about. We also have other targeted agents, so we have lenalidomide, REVLIMID, and also other IMiDs being studied in combination with bispecifics, and we think those should be maybe even rationally combined to the one potentiate. The other, lenalidomide, does help T-cells in some ways, helps NK cells in some ways as well, so maybe those could even give a greater than additive, a one plus one equals three kind of an efficacy. And we have a few studies of those completed in small groups, and now we're doing much bigger trials of lenalidomide plus bispecifics.