Therapeutic effect of T-cell engager in two patients with autoimmune neuropathy

Chronic immune-mediated peripheral nerve myelinopathies (CIPNM) are progressive and debilitating disorders that can be refractory to current treatment regimes. The bispecific T-cell engager (BiTE) teclistamab depletes B-cell Maturation Antigen (BCMA) positive late-stage B- cells and plasma cells by engaging T-cells. We present two patients with treatment-refractory CIPNM (Patient 1: IgM-kappa-associated CIPNM, follow-up 9 months; Patient 2: Anti-myelin-associated-glycoprotein (MAG) antibody-mediated CIPNM, follow-up 6 months). Both patients are characterized by rapid improvement upon treatment with teclistamab: substantially increased walking distance, accompanied by reduced nerve swelling and markedly improved electroneurography. Furthermore, some nerves without stimulus response at baseline are showing detectable response during follow-up. The functional recovery of peripheral nerves is paralleled by decreased serum neurofilament levels, indicating reduced neuronal damage. IgM kappa paraprotein and high-titer MAG antibodies are undetectable 6 weeks after the first dose of teclistamab and remain negative throughout the follow-up, whereas soluble BCMA re-emerges following an initial reduction. No serious adverse events are observed during treatment. This case series highlights the significant therapeutic potential of teclistamab in treatment-refractory CIPNM and provides an important example of 'off-the-shelf' BiTE therapy being well tolerated and effective and should be further investigated in neuro-immunological disorders.