SOHO 2021 | The future of CAR-T therapy

I think you heard me allude to where I want to see the field move, which is the use of CAR T-cell therapy in earlier lives, in particular, in the frontline setting. I didn’t mention earlier when I talked about unmet needs, but one of the major unmet needs is how do we address the fact that therapy for ALL is two and a half plus years long. That is a lot of therapy and it’s a slog. Again, especially for adults, they don’t tolerate the mercaptopurine and the methotrexate, even the vincristine, as well as our pediatric counterparts. They’re trying to hold jobs, finish their education, do all of those fundamental or participate in all those fundamental parts of life while experiencing frequent cytopenias, LFT aberrations, elevated bilirubins, you name it, trying to carry them through that long maintenance course. And that says nothing, by the way, of the toxicities they may experience just trying to get them through that initial induction consolidation, interim maintenance, delayed intensification phase. Our true treatment phase.

This has nothing of all the intrathecals. This has nothing of all those. I mean, again, they’re tough. They’re tough things to ask our adult patients to entertain. And when we try to sort of fast forward into the, again, the very elderly population, it gets even harder. I mean, how do you carry now, not a 20 year old, but a 60 year old or a 70 year old through each of these blocks of therapy? No, they don’t have to worry as much about career and family and education. But boy, the morbidity that they’re going to carry from each of the things that we do is going to be higher because their reserve is lower and their ability to bounce back from those therapies is going to be much less.

And so this, again, is where I see the earlier implementation of our novel agents. I didn’t mention it earlier, but I really liked this mini CBD inotuzumab, blinatumomab concept. It allows us to come in with a lower dose of inotuzumab. It allows us to consolidate with blina. I would ask the question now that we have the data from ZUMA-3 showing that those exposures to those agents don’t impact CAR T-cell responsiveness. I would make an argument that maybe that is a wonderful frontline approach.

Give your InO, give your blina. If you have MRD, or if you feel like this patient has high risk disease and you’re worried about their ability to tolerate transplant or they’re not, again, for all the reasons that transplant is difficult. What an optimal population now to begin thinking about CAR T-cell immunotherapy. Give one or two cycles of your mini InO, give a cycle of blina while you work to conduct your apheresis and your manufacturing of your CAR T-cell therapy, and then come in with your car. You’ve just shortened that therapeutic paradigm from years to a period of a few months. That’s powerful stuff. And from my perspective, that’s how I’d want to see CAR T-cell therapy evolve for this particular disease.