Objective:

N/A

Background:

Emerging literature has increasingly documented delayed movement and neurocognitive toxicity (MNT), manifesting as parkinsonism-like symptoms, following BCMA-targeted CAR-T therapy for relapsed/refractory multiple myeloma. This syndrome typically emerges at a median of 36 days post-infusion, clearly distinct from acute complications such as cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). Pathophysiologically, MNT is attributed to on-target effects of BCMA expression in the basal ganglia and substantia nigra, leading to dopaminergic neuron depletion, T-cell infiltration, and heightened CAR-T cell expansion in blood and cerebrospinal fluid.

Design/Methods:

N/A

Results:

We report a case of a 72-year-old man with relapsed/refractory IgA lambda multiple myeloma, who underwent multiple prior lines of therapy before receiving BCMA-targeted CAR-T cell infusion. Following infusion, he experienced mild grade 1 CRS, but no ICANS. Two weeks after, he began developing intention and rest tremors, unsteady shuffling gait, dysphagia to solids, apathy, and depression. Clinical examination revealed severe bradykinesia and cogwheel rigidity, postural instability, hypophonia, and orthostatic hypotension. Brain MRI showed myeloma-related marrow changes and nonspecific white matter hyperintensities. A dopamine transporter scan was unremarkable. He received high-dose dexamethasone with a prednisone taper. He showed poor response to sequential monotherapies, including carbidopa/levodopa, carbidopa/levodopa plus entacapone, ropinirole and rotigotine. Combination therapy with rotigotine, amantadine, and levodopa induced hallucinations. Midodrine improved orthostasis, but overall pharmacological response was minimal. Supportive interventions, including physical, occupational and speech-language therapy, were employed. The patient succumbed 9 months later to an unrelated small bowel obstruction complicated by sepsis.

Conclusions:

This case underscores MNT as a significant delayed complication of BCMA-directed CAR-T therapy, aligning with European Society for Blood and Marrow Transplantation (EBMT) guidelines. It emphasizes the need for extended neurological surveillance, recognition of limited dopaminergic therapy efficacy, early immunomodulatory interventions despite inconsistent results and involvement in registries to better elucidate prevalence, underlying mechanisms, and optimal management strategies.