BSH 2022 | CAR-T & bispecific antibodies in second-line DLBCL

So there’s been a lot of data recently over the last year or so in relapsed diffuse large B, most of it’s around cellular therapy and bispecific antibodies. So we’ve seen ZUMA-7 present and published now, which is looking at axi-cel in the first relapse of diffuse large B-cell lymphoma, and that showed a significant event-free survival advantage, and certainly a strong trend towards overall survival advantage.

But due to the crossover in the trial, it’s perhaps not too surprising, we haven’t seen an OS advantage develop. So I think we are really hoping that that will be licensed in Europe. It now is in the States, and reimbursed for second line treatment. That would be axi-cel because the BELINDA study that was looking at tisa-cel was negative.

So that I’m sure won’t be licensed, but we’re hoping that the axi-cel product will be. Yeah, so I think for those high-risk relapses, so primary refractory to R-CHOP or relapse within a year of treatment, because that’s where the study was looking at, we hope that we’ll move to CAR-T approach instead of having to give chemotherapy and aiming for an autologous transplant. Bispecifics are interesting. So bispecific antibodies, there’s several of them and they all look pretty active in the relapsed diffuse large B setting.

Many of us would like to use them as a bridge to CAR-T, because they’re relatively non-myelotoxic and quite well-tolerated. We would very much like to use them in CAR-T failure patients as well, but I should say none of these are licensed yet. We aren’t able yet to use them in routine clinical practice.

The major benefits of bispecific antibodies is they’re off-the-shelf. So, just stored in pharmacy, prescribing, give them the next day, which is very different from CAR-T cells where there’s a good six to seven to eight-week lag maybe as you’re organizing apheresis and then the product’s made and sent back and you’re giving chemo.

So there’s quite an unavoidable delay really, from CAR-T, to get CAR-T therapy. So that’s a major advantage of bispecifics. And another advantage I think is they’re going to be combinable with chemotherapy. So I’m sure we’re going to see bispecific plus R-CHOP trials, or maybe pola-R-CHP plus bispecific trials, looking to improve further that frontline space. So quite whereby specifics are going to find their home in diffuse large B, whether it’s frontline, first relapse, second relapse, third relapse, pre/post-CAR-T, I don’t think we know yet, but CAR-T I think is more defined. We hope we’ll really see that in the high-risk first relapse patients.