VIDEO: Treatment challenges in DLBCL care

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I said a lot of good things about immunotherapies, CAR T-cells by specific antibodies, let me say a concern or a shortcoming. They share sort of a common weakness, which is this thing called antigen escape and we are going to be seeing it more and more CD19 CAR T-cells, put patients into remission and when they relapse, there's a fair chance they can relapse with CD19-negative disease, CD20 bispecific antibodies, deep remissions.

Three, six months later, patients can relapse with CD20-negative disease. That's a real problem since we have a lot of other agents that also target those same targets. You know, we have ADCs against CD19. We have lots of therapies against CD20. If the target's gone, that's a real problem, so we have some ways to try to treat these patients. If their tumors demonstrate antigen escape, use a different target. Go after CD22. Go after CD79. But really, I feel a little strongly about this, but we should be focused more on not treating antigen escape, but preventing it.

They're using rational combinations from the get go. Try specific antibodies that target CD20 and CD79 at the same time to try to prevent patients from just showing up with CD20-negative disease 'cause the CD79 component could still hopefully induce remissions. Preventing antigen escape that way or with other rational combinations that we chatted about, small molecule inhibitors, other immunomodulators and we're working in the lab on some other ways to try to develop more effective CAR T-cells, maybe more effective bispecific antibodies that will be able to kill those CD20-negative cells before they manifest in antigen-negative relapse.

So antigen escape is gonna be actually a bigger problem over the next decade than it has been before because immunotherapies are good, so they will more powerfully enrich for the CD20-negative cells, for example. So we're gonna have a lot of this problem over the next few years and we're gonna have to be working on ways to treat it, but also to prevent it.