Abstracts
PO60
First Recorded Case of LCMV Meningoencephalitis Complicating Teclistamab Therapy: Successful Diagnosis and Treatment
Introduction/Background/Significance:
Materials and Methods/Case Presentation/Objective:
Brain MRI demonstrated diffuse leptomeningeal enhancement with bilateral cranial nerve VII/VIII involvement. CSF analysis showed lymphocytic pleocytosis, markedly elevated protein, and hypoglycorrhachia. Extensive microbial, autoimmune and malignant investigations were negative. Despite empirical antibacterial, antifungal and antituberculous treatment, neurological deterioration continued. Stereotactic brain biopsy was non-diagnostic, demonstrating non-specific inflammatory changes.
Metagenomic next-generation sequencing (mNGS) of CSF subsequently identified LCMV, confirmed by targeted RT-PCR in CSF, blood, urine and brain tissue. Retrospective history identified significant domestic mouse exposure. Given the paucity of evidence-based therapies for LCMV infection, a multi-institutional group of virologists recommended a combination antiviral therapy comprising remdesivir, ribavirin and favipiravir. Treatment continued for 72 days during inpatient stay. Favipiravir dosing was optimised using serum and CSF therapeutic drug monitoring. At discharge, the patient continued favipiravir and ribavirin, transitioning to favipiravir monotherapy after 117 days of antiviral therapy owing to ribavirin-induced anaemia. Favipiravir was stopped after a total of six months of treatment.
Results/Description/Main Outcome Measure(s):
Conclusion(s).:
Trademarked Items:
References:
BCMA-directed bispecific antibodies have transformed the treatment of RRMM, but induce prolonged humoral and cellular immune dysfunction, predisposing patients to opportunistic infections. Lymphocytic choriomeningitis virus (LCMV) is a rare rodent-borne arenavirus that causes meningoencephalitis in immunocompromised hosts with high mortality. We report the first documented case of LCMV associated with bispecific treatment, describing its diagnosis and successful management.
Materials and Methods/Case Presentation/Objective:
A 60-year-old man with lambda light-chain RRMM achieved a sustained complete biochemical response on teclistamab following seven prior lines of therapy, including immunomodulatory agents (IMiDs), proteasome inhibitors (PIs), an anti-CD38 monoclonal antibody and an autologous stem-cell transplant. His treatment course was complicated by a previous disseminated adenovirus infection in the context of severe hypogammaglobulinaemia, requiring monthly IVIG replacement.
After more than two years of teclistamab therapy, he presented with a five-month history of progressive headache, bilateral hearing loss, gait ataxia, cognitive impairment and weight loss. Teclistamab treatment was discontinued at the point of presentation.
Brain MRI demonstrated diffuse leptomeningeal enhancement with bilateral cranial nerve VII/VIII involvement. CSF analysis showed lymphocytic pleocytosis, markedly elevated protein, and hypoglycorrhachia. Extensive microbial, autoimmune and malignant investigations were negative. Despite empirical antibacterial, antifungal and antituberculous treatment, neurological deterioration continued. Stereotactic brain biopsy was non-diagnostic, demonstrating non-specific inflammatory changes.
Metagenomic next-generation sequencing (mNGS) of CSF subsequently identified LCMV, confirmed by targeted RT-PCR in CSF, blood, urine and brain tissue. Retrospective history identified significant domestic mouse exposure. Given the paucity of evidence-based therapies for LCMV infection, a multi-institutional group of virologists recommended a combination antiviral therapy comprising remdesivir, ribavirin and favipiravir. Treatment continued for 72 days during inpatient stay. Favipiravir dosing was optimised using serum and CSF therapeutic drug monitoring. At discharge, the patient continued favipiravir and ribavirin, transitioning to favipiravir monotherapy after 117 days of antiviral therapy owing to ribavirin-induced anaemia. Favipiravir was stopped after a total of six months of treatment.
Results/Description/Main Outcome Measure(s):
Persistent neurological recovery was observed on combination antiviral therapy and was well tolerated. LCMV RNA became undetectable in CSF, blood and urine within two months of treatment initiation. Within six months of antiviral treatment, the patient regained independent mobility, returned to employment, and was left with only mild residual neurological symptoms. Fourteen months after discontinuing teclistamab, he remains in complete biochemical remission from myeloma without additional anti-myeloma therapy or evidence of recurrent LCMV infection.
Conclusion(s).:
This is the first reported case of LCMV meningoencephalitis associated with bispecific antibody therapy and expands the spectrum of opportunistic infections associated with teclistamab-induced immune dysfunction. The case demonstrates that LCMV remains a cause of rare neurotropic viral infections in the UK and should be considered in immunosuppressed patients who present with unexplained neurological syndromes, particularly when conventional investigations are unrevealing. It also highlights the diagnostic value of mNGS in identifying unexpected pathogens and advocates for its utility for immunocompromised individuals where such pathogens are more frequent. Finally, we describe a novel treatment regimen of combination antivirals that achieved virological clearance and favourable neurological recovery in persistent LCMV infection.
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