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EHA 2026 | CD22-directed CAR-T for NHL subtypes: toxicity and sequencing insights
Matthew Frank, MD, PhD, Stanford University, Stanford, CA, shares insights into the safety of CD22-directed CAR T-cell therapy in non-Hodgkin lymphoma (NHL) subtypes, noting that the reason for its favorable toxicity profile remains unknown. Dr Frank highlights that CD22-directed CAR-T therapy is currently being explored mostly in CAR-exposed patients, who represent a significant clinical unmet need. This interview took place at the 31st Congress of the European Hematology Association (EHA) in Stockholm, Sweden.
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Transcript
So I think this is a great question. So as you’re pointing out, we see very little neurotoxicity after a CD22-directed CAR. That’s both seen in the data we’re presenting here at EHA and in prior trials. And to be really honest with you, we don’t know why. It’s just what we’ve seen clinically. We’ve looked at cytokines and see if there’s a different pattern...
So I think this is a great question. So as you’re pointing out, we see very little neurotoxicity after a CD22-directed CAR. That’s both seen in the data we’re presenting here at EHA and in prior trials. And to be really honest with you, we don’t know why. It’s just what we’ve seen clinically. We’ve looked at cytokines and see if there’s a different pattern. So far we don’t see much that’s clinically relevant. It’s an area of ongoing investigation. There is a little bit of data that suggests that CD19 and BCMA are expressed within brain tissue, and we don’t see a lot of CD22 expression in brain tissue. So that may be one hint, but I don’t think that explains it all. There are still very early days for the CD22-directed CAR therapy. It’s been mostly tested in CAR-exposed patients. And there, there’s a huge unmet need, particularly in large B-cell. Median survival is probably well under a year. Even bispecifics, which are very effective, don’t particularly work within a few months after CAR therapy. So for now, I think the CD22-directed CAR therapy should be after a pre-existing CAR. And I think it somewhat should be guided based on the personal profile of the patient. There are patients who lose CD19 and CD20, but retain CD22 expression. So for patients who lose the target or have mutations in the target of CD19, I think CD22 is a very viable option.
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