SOHO 2025 | The development of predictive biomarkers for bispecifics, CAR-T, or ADCs in lymphoma

Yeah, I think that’s been a bit more of a difficult space. I think what we’ve seen, at least with the bispecifics, with what we have currently available, I would say if they don’t express CD20, then we’re not likely to get a response. And so I think that CD20 expression is probably the most likely predictive biomarker. And a lot of us have suspicions that a lot of the progression or relapses, at least in the mantle cell lymphoma space at least with glofitamab has been driven by loss of CD20 expression. Now whether that’ll be the same with mos and po because we’re targeting two different antigens will be up for debate and something we’ll have to see. With the CAR T-cell therapy, if we can look at the current data, the most predictive sort of biomarker I would say is not really a biomarker but what the patient has received previously. And all of the two approved CAR T-cell products we do see a discordance and response based on BTK inhibitor exposure. So with brexu-cel we do see that at least post-ibrutinib the efficacy seems comparable to a BTK naive patient population, but in the small patients who received the second-generation BTK inhibitors, the response rate and duration of response was quite inferior to what we saw in the BTK naive and what we saw in patients exposed to ibrutinib. Now with liso-cel, overall the post-BTK space, there is a wide gap between the duration of response, progression-free survival for those who had seen the BTK inhibitor versus those who didn’t, suggesting that there is some change in biology that maybe makes liso-cel not as effective in those post-BTKi patients. With the ADCs, obviously, there has been a push now with the ROR1 ADC and there are more coming down the line. But in this situation, I don’t necessarily know we have specific biomarkers per se that are predicting responses to the ADCs. I will say encouragingly enough, it doesn’t appear that p53 is a negative predictive biomarker for the CAR T-cell therapies or the bispecifics. They seem to be agnostic to p53 expression. Now, we need more information about blastoid pleomorphic variants because, again, these patients have a rapidly progressive disease, the elevated Ki-67. So whether these patients have equivalent responses, whether the blastoid pleomorphic variant is present or not, it’s something that will need to be looked at. Then I’m sure we’re trying to dig into other biomarkers to see if they are predictive or not of response to these treatments. Because again, as of right now, these are our best salvage options post-BTKi in this patient space.

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