Bordetella holmesii Meningoencephalitis During Teclistamab Therapy for Relapsed/Refractory Multiple Myeloma

Teclistamab, a B-cell maturation antigen (BCMA)-directed bispecific antibody, has expanded treatment options for relapsed or refractory multiple myeloma (RRMM), but is associated immune and infectious complications. Fever and neurologic symptoms in patients receiving teclistamab may also raise concern for infections, cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS), creating a diagnostic challenge.

A 54-year-old man with RRMM receiving teclistamab as fifth-line therapy presented with several weeks of progressive somnolence, intermittent confusion, abnormal movements, poor oral intake, and recurrent fevers. Teclistamab had been initiated approximately 7 months earlier, and his most recent dose was 4 weeks before presentation. Initial evaluation demonstrated leukopenia without neutropenia, severe thrombocytopenia, anemia, lymphopenia with an absolute lymphocyte count of 0.38 × 10⁹/L, and profound hypogammaglobulinemia with IgG < 40 mg/dL. Continuous video electroencephalography showed generalized slowing without seizures. Lumbar puncture was delayed because of thrombocytopenia and performed on hospital day 8. Cerebrospinal fluid (CSF) analysis showed glucose 10 mg/dL, protein 3086 mg/L, and 196 nucleated cells/mm³ with mixed neutrophilic and lymphocytic pleocytosis. Bacterial, fungal, and acid-fast bacilli cultures were negative, and a meningitis/encephalitis nucleic acid panel was unrevealing. Brain magnetic resonance imaging (MRI) demonstrated scattered leptomeningeal enhancement, a micro-septated appearance within the bilateral parietal sulci, and progressive ventricular enlargement concerning for ventriculitis with communicating hydrocephalus. Blood cultures from multiple sets grew Bordetella holmesii, and plasma microbial cell-free DNA testing also detected B. holmesii. Although recurrent CRS and ICANS were considered, the delayed timing after teclistamab exposure, subacute progression, inflammatory CSF profile, neuroimaging findings, and bacteremia favored infectious meningoencephalitis with ventriculitis. Corticosteroids were deferred. The patient received broad-spectrum antimicrobials followed by meropenem 2 g intravenously every 8 hours for a planned 2-week course, along with intravenous immunoglobulin for severe hypogammaglobulinemia. His fevers resolved, myoclonus improved, and mental status gradually recovered. Follow-up brain MRI approximately 1 month after discharge demonstrated interval improvement in the leptomeningeal enhancement and micro-septated sulcal abnormalities.

To our knowledge, this is the first reported case of B. holmesii central nervous system infection during BCMA-directed bispecific antibody therapy. In patients receiving teclistamab who develop fever, encephalopathy, or abnormal movements, CRS and ICANS should remain considerations, but they should not delay evaluation for infection. Early blood cultures, CSF analysis, neuroimaging, consideration of atypical pathogens, and assessment of humoral immune deficits may be critical to timely diagnosis and management.