Neurocognitive and hypokinetic movement disorder with features of parkinsonism after BCMA-targeting CAR-T cell therapy

Abstract

Brief CommuniCation Nature MediciNeExtended Data Fig. 10 | immunohistochemistry showing BCMA protein expression in brain tissue of the patient and in a control brain. (a) BCMA immunohistochemistry of the caudate nucleus subependymal region (10x magnification, left, scale bar 200 µm). Inset (40x magnification, right, scale bar 50 µm) shows high magnification image of astrocytes (top) and a neuron (bottom) that stained positive for BCMA, whereas surrounding cells were negative. Images shown are representative slides from the caudate nucleus from the patient described in this case report (N = 1). For each region stained, at least 3 slides were available. (b) BCMA immunohistochemistry of selected brain regions as annotated in the patient of interest (left) versus a control brain (right) from a subject who died due to non-neurologic illness (10x magnification (top), scale bar 200 µm and 20x magnification (middle, bottom), scale bar 100 µm). Images shown are representative slides from the patient described in this case report (N = 1), as well as a single control brain (N = 1). For each region stained, at least 3 slides were available. The experiment was repeated in a second control brain with similar results.

Comprehensive BCMA Expression Profiling in Adult Normal Human Brain Suggests a Low Risk of On-target Neurotoxicity in BCMA-targeting Multiple Myeloma Therapy

“…However, that article did not present details on the development of their assay, such as staining results from orthogonally qualified BCMA-positive and BCMA-negative control samples, which would be needed to rule out nonspecific immunoreactivity. 24 As the mechanism underlying neurological symptoms remains undefined, evaluation of a large number of brain samples from myeloma patients with neurological symptoms is needed; however, the absence of BCMA protein detection in the present data suggests a low risk of direct on-target/ off-tumor cytotoxicity in the brain.…”

“…A recent case report described a patient who was treated with an anti-BCMA CAR-T therapy (ciltacabtagene autoleucel) and had neurological adverse events, including a movement disorder consistent with parkinsonism. 24 The authors examined this patient and one healthy subject and reported BCMA expression in neurons and astrocytes in the caudate nucleus, using a rabbit polyclonal antibody (US Biological B0807-50). However, that article did not present details on the development of their assay, such as staining results from orthogonally qualified BCMA-positive and BCMA-negative control samples, which would be needed to rule out nonspecific immunoreactivity.…”

CAR-T cells for the treatment of relapsed/refractory multiple myeloma in 2022: efficacy and toxicity

“…Acute cerebral edema is probably the most serious and potentially life-threatening complication which was described after treatment with CAR T-cells against CD-19 [64]. Very delayed symptoms, such as progressive movement disorder with features of Parkinsonism approximately 3 months after infusion of CAR-T, were described also [65].…”

Harnessing the T Cell to Treat Multiple Myeloma: Dawn of a New Therapeutic Paradigm

“…This other neurotoxicity occurred later with a median onset of 27 days with variable associate symptoms including a cluster of movement and neurocognitive treatment-emergent events. Further exploration to understand and minimize the frequency to this other neurotoxicity is ongoing and a recent description of BCMA expression on neurons and astrocytes in the basal ganglia may represent a possible mechanistic explanation (116). Most cases of ICANS can be managed successfully with a short course of corticosteroids.…”