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News
As GPRC5D-targeted therapies like talquetamab gain traction in multiple myeloma, clinicians are spotting a troubling pattern: cerebellar toxicity. Symptoms range from dizziness and slurred speech to balance and gait problems — and they can persist for years. With no standardized definition or proven management strategy yet, experts are calling for urgent research and better clinical recognition.
As more patients with BCMA-resistant multiple myeloma turn to GPRC5D-targeted therapies — including the FDA-approved bispecific antibody talquetamab and several CAR T-cell therapies in the pipeline — a poorly understood neurological complication is coming into focus: cerebellar toxicity. Symptoms include dizziness, dysarthria (slurred speech), ataxia, and gait and balance disturbances, and they can be easy to miss or misattribute to side effects from prior treatments like bortezomib.
The condition appears to be antigen-specific (not seen with BCMA-directed therapies), likely immune-mediated, and dose-dependent with CAR T-cell products. Onset timing varies — earlier with CAR T-cell therapy (around 30 days) and later with bispecific antibodies (often from cycle 7 onward). Troublingly, symptoms can persist: roughly 40% of patients in the MonumenTAL-1 trial had ongoing symptoms, and some showed lasting effects three years out.
By the Numbers:
Why it matters: With talquetamab expected to move into earlier treatment lines, the patient population exposed to this risk will grow significantly. Clinicians need a formal definition, standardized screening tools, and evidence-based management protocols — none of which currently exist.
