Mosunetuzumab-associated fatal HHV-6 encephalitis in a patient with follicular lymphoma

Introduction Mosunetuzumab is a CD3×CD20 bispecific antibody approved for relapsed/refractory follicular lymphoma. Although it was shown to achieve high response rates and durable remissions, immunosuppression with its use can be significant. Immune effector cell–associated neurotoxicity syndrome (ICANS) has been described with bispecific T-cell engager (BiTE) therapies, but human herpesvirus-6 (HHV-6) encephalitis has not been previously reported. Case We describe a 76-year-old woman with grade 3A follicular lymphoma treated with mosunetuzumab for twelve weeks. Ten days after the 4th cycle, she was admitted to the hospital with gradual onset of confusion and generalized weakness. Magnetic resonance imaging (MRI) showed bilateral mesial temporal T2/FLAIR hyperintensities. Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) testing revealed HHV-6 infection. Management and outcome ICANS was initially suspected, and dexamethasone 10 mg IV daily was started. Following positive PCR testing for HHV-6, IV ganciclovir was commenced. Despite aggressive antiviral treatment, the patient's condition deteriorated and she died on hospital day 12. Discussion/conclusion Symptomatic HHV-6 reactivation has been recorded in the setting of allogeneic stem cell transplant and chimeric antigen receptor (CAR) T-cell therapy. This is the first instance of HHV-6 encephalitis associated with mosunetuzumab. The case underscores the importance of early CSF analysis and neuroimaging in patients with encephalopathy receiving T-cell–engaging therapies.