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OBJECTIVE: To describe the specific complication of motor aphasia seen in a small minority of patients treated with CD19-targeted CAR therapy. BACKGROUND: CD19-targeted, genetically-modified autologous T-cell infusions are increasingly used to treat hematologic malignancies. Complications of immunotherapy are known to include cytokine storm with hypotension and encephalopathy. Focal neurological deficits have not been reported to be part of this syndrome despite successful treatment with CD19 CAR in multiple centers. DESIGN/METHODS: Three patients are described with regards to the specific complication of motor aphasia; other less focal neurological outcomes will be described elsewhere. Allen Brain Atlas was searched for CD19-probe expression in donor brains. RESULTS: Three patients out of 21 treated with CD19-targeted CAR developed motor aphasia 4-5 days after receiving CD19 CAR cells, following chemotherapy pre-treatment, progressing in two patients to generalized encephalopathy. One patient progressed to global aphasia and mild right face and arm weakness; one patient progressed to hyperreflexia and generalized myoclonus before becoming obtunded; one patient also had hemifacial spasm and progressed to encephalopathy. In all three patients aphasia and other neurological symptoms resolved over days and no correlative changes were seen on MRI or EEG. Data was available for expression of 2 CD19 probes in 6 donor human brains in the Allen Brain Atlas. Of these, one brain showed a higher expression of CD19 in the left inferior frontal gyrus. CONCLUSIONS: CD19-targeted CAR therapy can lead to a number of neurological complications, including a motor aphasia in some. CD19 may be expressed in a subset of neurons but is clearly variable between individual subjects, as evidenced by probe data in the Brain Atlas. Preferential expression in the language areas in some patients, for CD19 or related cytokines or other components of the CAR construct, may explain why reversible motor aphasia may complicate CD19 CAR immunotherapy in a small minority of patients. Study Supported by: This research was supported by the NIH Intramural Program.
Kranick et al. (Tue,) studied this question.