Patients with multiple myeloma experience neurologic manifestations from paraprotenemia or direct central nervous system invasion. With advances in myeloma therapies, drug-associated neurotoxicities are also emerging. Daratumumab is an anti-CD38 monoclonal antibody that induces targeted cell death and a highly effective myeloma therapy. Case reports have suggested leukoencephalopathy as a late adverse event. We describe a patient with multiple myeloma on daratumumab therapy that developed acute leukoencephalopathy that resolved following treatment.

A 44 year-old female with multiple myeloma on weekly daratumumab, bortezomib and methylprednisolone initiated two months prior presented with acute right facial weakness, numbness, slurred speech, and short-term memory deficits. Neuroimaging demonstrated amorphous restricted diffusion in the left centrum semiovale, without contrast enhancement or T2 hyperintensity. Vessel imaging and additional stroke workup were negative. Symptoms resolved without intervention by day 2, but on day 7 she experienced an acute worsening with more severe slurred speech, new left facial numbness, weakness, and leftward tongue protrusion. Repeat neuroimaging showed that the prior lesion demonstrated T2 hyperintensity without enhancement and new right centrum semiovale restricted diffusion. Cerebrospinal fluid (CSF) demonstrated 5 nucleated cells (95% lymphocytes, predominantly T-cells without monoclonality), normal protein and glucose, and negative viral PCRs. CSF myelin basic protein was normal. There was a distinct CSF IgG kappa monoclonal band, which likely represented the daratumumab molecule, raising suspicion for early onset daratumumab-associated leukoencephalopathy. High dose IV methylprednisolone and IVIg were administered. Her slurred speech and facial numbness improved. Daratumumab and bortezomib were discontinued, and prednisone taper and monthly IVIg were planned. One month later, she remained symptom free with improved neuroimaging.

Daratumumab-associated leukoencephalopathy is a rare but important adverse event. Early clinical suspicion, timely discontinuation of daratumumab, and antibody-mediated treatments like IVIg can prevent irreversible neurologic injury.