Objective:

NA

Background:

Chimeric antigen receptor (CAR) T-cell therapy is a modern targeted immunotherapy used to treat cancer and autoimmune disease. Although autoimmune conditions have been rarely reported after CAR-T, new-onset multiple sclerosis (MS) has not previously been described.

Design/Methods:

NA

Results:

A 63 year old male with a history of B-cell lymphoma status post rituximab and CAR-T therapy (axicabtagene ciloleucel, Yescarta) two years prior, presented with right eye vision loss followed by left eye vision loss several weeks later. MRI revealed contrast enhancement of the right optic nerve as well as a chronic demyelinating lesion in the cervical spinal cord and an active demyelinating lesion in the thoracic spinal cord. Two lumbar punctures demonstrated normal protein and cell counts, negative flow cytometry and cytology, matched oligoclonal bands in serum and CSF. Negative serum studies including aquaporin-4 and MOG antibodies (x3), serum paraneoplastic antibody panel including CRMP5, ANA 1:40, ANCA and dsDNA, infectious studies, and normal ESR/CRP. He fulfilled criteria for dissemination in time and space, consistent with MS. Treatment included IV methylprednisolone and plasma exchange, resulting in some improvement over 4 weeks. Outpatient initiation of rituximab was planned.

Conclusions:

Although CAR-T therapy is being investigated as a potential treatment for severe, refractory MS, new-onset MS following CAR-T has not been reported. Documented autoimmune sequelae include Hashimoto’s thyroiditis, though the underlying mechanisms remain poorly understood. A plausible mechanism parallels the paradoxical autoimmune exacerbations seen with B-cell-depleting agents such as rituximab. Sustained B-cell depletion, may diminish regulatory B cells that normally suppress T-cell-mediated autoimmunity, and through this these therapies may facilitate autoimmune disease through a similar mechanism. CAR-T therapy may not be a final therapy for MS, because once B-cell populations rebound, MS activity may rebound. Though further studies are needed to explore these theories.