TOPLINE:

Teclistamab therapy in patients with refractory autoimmune diseases led to drug-free remission in 6 of 10 patients. Cytokine release syndrome was mild and manageable with tocilizumab.

METHODOLOGY:

• T-cell engagers redirect T-cell activity for targeted cell depletion. Researchers assessed the safety and efficacy of teclistamab, a bispecific antibody that targets CD3 on T cells and B-cell maturation antigen on B cells and plasma cells.
• The study involved 10 patients with six different refractory autoimmune diseases (median age, 55 years; 60% female) who were followed up for up to 15 months; the patients included three with systemic sclerosis, one with primary Sjögren disease, two with idiopathic inflammatory myositis, one with rheumatoid arthritis, one with Graves disease, and two with immunoglobulin G4-related disease.
• Patients did not respond to treatment with more than three immunomodulatory drugs; glucocorticoids were tapered to < 5 mg/d, and all other immunosuppressive medications were discontinued before receiving teclistamab under compassionate use.
• Teclistamab was administered in a step-up dosing regimen over 5 days in an inpatient setting, starting with 0.06 mg/kg on day 1, 0.3 mg/kg on day 3, and 1.5 mg/kg on day 5, followed by a single maintenance dose of 1.5 mg/kg after 4 weeks.
• B-cell depletion, the occurrence of cytokine release syndrome, and changes in levels of disease-specific autoantibodies were monitored.

TAKEAWAY:

• Teclistamab induced B-cell depletion, with a median duration of B-cell aplasia of 157 days; all patients had free kappa- and lambda-light chains below detection levels.
• Cytokine release syndrome was observed in 8 of 10 patients within 2 days of receiving teclistamab but was mild and manageable with tocilizumab. No grade 3 or 4 cytokine release syndrome or neurotoxicity was reported.
• All patients developed hypogammaglobulinemia, with a median onset of 4 weeks post-therapy, and were treated with immune globulin infusions. Patients treated with teclistamab also experienced a decrease in levels of disease-specific autoantibodies.
• Symptoms were alleviated and diffusion capacity increased in four of five patients with interstitial lung disease, with one experiencing worsening. Six of seven patients were off glucocorticoids at the latest follow-up, and 8 of 10 patients were not on immunosuppressants.

IN PRACTICE:

“Teclistamab appeared to show durable efficacy as rescue therapy across six different refractory autoimmune diseases,” the authors of the study wrote. “Further clinical trials are warranted to better understand the safety and efficacy of teclistamab for refractory autoimmune disease,” they added.

SOURCE:

This study was led by Laura Bucci, MD, Friedrich Alexander Universität Erlangen-Nürnberg, Erlangen, Germany. It was reported online on October 16, 2025, in a letter to the editor published in The New England Journal of Medicine.

LIMITATIONS:

No limitations were discussed in the correspondence.

DISCLOSURES:

The study was supported by grants from the Deutsche Forschungsgemeinschaft, Else Kröner-Fresenius Foundation, Lupus Research Alliance, Boehringer Ingelheim Foundation, IZKF Erlangen, and other sources, with additional funding from other sources. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.