The bispecific B-cell maturation antigen-targeted antibody teclistamab induced remission in a patient with refractory systemic lupus erythematosus after failing to respond to multiple prior therapies and demonstrated potential in treating other refractory autoimmune diseases unresponsive to conventional therapies, according to recent letters and case reports. 

Two case reports highlighted its potential by targeting B cells and plasma cells through CD3 and B-cell maturation antigen (BCMA), offering an alternative to chimeric antigen receptor (CAR) T-cell therapies.

In the first case report, published in the New England Journal of Medicine, a 23-year-old woman with severe, refractory lupus and lupus nephritis achieved remission without the need for ongoing medication following treatment with teclistamab. The patient, whose disease was resistant to multiple therapies, including hydroxychloroquine, mycophenolate mofetil, and belimumab, received five doses of teclistamab. Following treatment, she demonstrated improvement, with a reduction in proteinuria, an increase in hemoglobin levels, and a decrease in the Systemic Lupus Erythematosus Disease Activity Index. B cells and plasma cells were rapidly depleted, and anti–double-stranded DNA (dsDNA) antibodies decreased to undetectable levels. Adverse events included mild cytokine release syndrome and hypogammaglobulinemia, both of which were mild to moderate and observed without significant complications.

The patient's protein-to-creatinine ratio in urine dropped from 2,352 mg/g to under 500 mg/g by week 6 of treatment. Hemoglobin levels also showed improvement during the teclistamab course. Anti–dsDNA antibody levels decreased from 2,440 IU/mL to within the normal range by week 5 and remained undetectable through week 16. Peripheral blood B cells were reduced by week 1, and bone marrow plasma cells and B cells were eliminated by week 8. Reported adverse events included Grade 2 cytokine release syndrome, pneumonia, sinusitis, and hypogammaglobulinemia.

In the second case report, published in the New England Journal of Medicine, 4 patients with various refractory autoimmune diseases—systemic sclerosis, primary Sjögren syndrome, idiopathic inflammatory myositis, and rheumatoid arthritis—were treated with escalating doses of teclistamab. All of the patients had failed more than five prior immunosuppressants, including rituximab. Teclistamab demonstrated clinical efficacy across this cohort, with reductions in disease activity scores, inflammation, and autoantibody levels. The treatment resulted in mild to moderate adverse events, including cytokine release syndrome and manageable infections.

Teclistamab doses were gradually increased from 0.06 mg/kg on day 1 to 1.5 mg/kg by day 5. In terms of disease improvement, the Modified Rodnan skin score in the patient with systemic sclerosis decreased from 39 to 24. The EULAR Sjögren’s Syndrome Disease Activity Index score in the patient with Sjögren’s syndrome dropped from 34 to 15. The patient with idiopathic inflammatory myositis had a Cutaneous Dermatomyositis Disease Area and Severity Index score reduction from 22 to 6, and the patient with rheumatoid arthritis saw a decrease in their DAS28-CRP score from 5.9 to 1.9. Adverse events included mild to moderate cytokine release syndrome (Grades 1 and 2), along with four reported infections, including viral gastroenteritis, cutaneous infection, herpes labialis, and an upper respiratory tract infection.

While the initial results are promising, the studies emphasized the need for larger trials to assess the long-term safety and efficacy of teclistamab. Nonetheless, the researchers concluded that teclistamab may offer a novel approach for targeting the plasma cell compartment in autoimmune diseases. 

Full disclosures can be found in the published letters.