Teclistamab Shows Promise in Refractory Autoimmune Diseases

TOPLINE: 

Teclistamab, a T-cell engager that targets B-cell maturation antigen (BCMA), improved disease activity in four patients with refractory autoimmune conditions. In a separately published case report, teclistamab treatment induced remission in a patient with refractory systemic lupus erythematosus (SLE).

BACKGROUND: 

• Chimeric antigen receptor (CAR) T cells or T-cell engagers against CD19 have been effective in small studies of patients with treatment-resistant autoimmune diseases.
• Some patients have disease rooted in long-lived plasma cells that express BCMA but not CD19, making them resistant to CD19 CAR T-cell therapy.
• Teclistamab acts on T cells through CD3 and targets plasmablasts and plasma cells through BCMA.

METHODOLOGY:

• In one case series, researchers administered teclistamab subcutaneously to four patients with autoimmune diseases resistant to more than five immunosuppressants, including rituximab.
• Patient 1 had systemic sclerosis, patient 2 had primary Sjögren disease, patient 3 had idiopathic inflammatory myositis, and patient 4 had rheumatoid arthritis.
• Researchers incrementally increased teclistamab dosage in an inpatient setting: 0.06 mg/kg on day 1, 0.3 mg/kg on day 3, and 1.5 mg/kg on day 5. Patients 2, 3, and 4 received one maintenance dose of 1.5 mg/kg after 4 weeks, and patient 1 received a 1.5-mg/kg dose after 12 weeks.
• In the single case report, the patient with SLE received a step-up dosage of teclistamab (0.06 mg/kg and 0.3 mg/kg) followed by 0.8 mg/kg on day 7. She received 1.5 mg/kg at weeks 2 and 5.

TAKEAWAY: 

• Teclistamab therapy led to significant improvements in disease activity in all four patients, with notable reductions in skin disease, arthritis, and lung function scores.
• Teclistamab therapy had a good safety profile, with no neurotoxicity or myelotoxicity and only lower-grade cytokine release syndrome reported.
• Researchers observed seroconversion of PM-Scl-75, PM-Scl-100, rheumatoid factor, and autoantibodies against mutated citrullinated vimentin and lower levels of autoantibodies ANA, MDAS, SS-A/Ro, SS-B/La, and PL-7 after treatment.
• In the separate case report, the patient reached complete drug-free remission by week 6, as defined by the Systemic Lupus Erythematosus Disease Activity Index 2000.
• The level of anti-double–stranded DNA antibodies in the patient with SLE decreased rapidly, reaching normal range by week 5 and remaining undetectable through week 16.

IN PRACTICE:

“These data show that the targeting of the plasma-cell compartment by a BCMA-targeted T-cell engager is feasible in patients with autoimmune disease. Whether such therapy results in sustained clinical remission warrants further study,” write the authors of the four-patient case series.

SOURCE: 

Melanie Hagen, MD, Friedrich Alexander University Erlangen–Nuremberg, Germany, and colleagues reported their case series online on September 4 in the New England Journal of Medicine. Tobias Alexander, MD, and colleagues at Charité–Universitätsmedizin Berlin, Germany, also described their single case report online on September 4 in the New England Journal of Medicine.

LIMITATIONS:

The small number of patients limits the generalizability of the findings. The short duration of follow-up may not capture long-term effects and potential late-onset adverse events. The lack of a control group makes it difficult to attribute improvements solely to teclistamab therapy.

DISCLOSURES:

The four-patient case series was supported by grants from the Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, and the European Union. The single case report was supported by grants from the Deutsche Forschungsgemeinschaft and the European Union. Several authors have disclosed financial relationships with pharmaceutical companies, including Janssen Biotech, which markets teclistamab.

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