TOPLINE

Teclistamab (Tecvayli), a B-cell maturation antigen-directed bispecific antibody, induced major clinical responses in more than 60% of patients with severe treatment-refractory autoimmune diseases. However, cytokine release syndrome (CRS) occurred frequently, and the treatment was associated with hypogammaglobulinemia and frequent infections.

METHODOLOGY

• Researchers retrospectively collected data from 18 patients (median age, 48.5 years; 72% women) with treatment-refractory autoimmune diseases such as systemic sclerosis (n = 10), idiopathic inflammatory myopathies (n = 4), systemic lupus erythematosus (n = 2), undifferentiated connective tissue disease (n = 1), or immunoglobulin G4 (IgG4)-related disease (n = 1) who received teclistamab at five specialized centers in Europe between March 2024 and October 2025.
• Teclistamab was administered subcutaneously in a step-up regimen on the basis of the approved schedule for multiple myeloma, with a median of four target doses of 1.5 mg/kg and a median cumulative dose of 6.36 mg/kg over a median of six injections during a median period of 28 days.
• All patients received prophylaxis with acyclovir and co-trimoxazole after the first teclistamab injection and prophylactic intravenous Ig replacement therapy when serum IgG levels dropped < 4 g/L.
• Patients were monitored under inpatient observation for at least 48 hours after step-up doses and the first target dose, with follow-up safety visits scheduled every 2-4 weeks within the first 6 months, then every 4-8 weeks, to assess for CRS and immune effector cell-associated neurotoxicity syndrome.

TAKEAWAY

• A total of 22 CRS episodes (16 grade 1 and 6 grade 2) occurred in 12 patients (67%), with their incidence declining with repeated injections; 91% of cases occurred within 2 days after the last teclistamab injection. No cases of immune effector cell-associated neurotoxicity syndrome were observed.
• Infections were observed in 67% of patients, with upper respiratory tract infections being the most common. Five patients required hospitalization for seven events necessitating intravenous antibiotic treatment, mainly due to early respiratory infections, and four severe infections related to treatment delays occurred within the first 4 weeks after treatment initiation.
• Teclistamab induced peripheral B-cell depletion in all patients, with initial B-cell recovery > 0.01 cells/nL of blood occurring at a median of 20.0 weeks in 10 patients, and normal levels > 0.1 cells/nL of blood were reached by four patients at a median of 43.6 weeks. All patients with available follow-up developed severe hypogammaglobulinemia, with IgG levels < 4 g/L occurring at a median of 8.9 weeks; 89% were administered intravenous Ig replacement therapy.
• Two patients developed severe noninfectious colitis. Major clinical responses were achieved in 61% of patients, and minimal-to-moderate responses were achieved in 22%, with a median time to moderate and major responses of 3.9 and 8.1 weeks, respectively.

IN PRACTICE

“Our findings support further evaluation of teclistamab as a potential treatment for highly selected patients with severe, treatment-refractory connective tissue diseases. Clinically significant adverse events, including infections related to hypogammaglobulinemia and fatal events in patients with advanced cardiac involvement, underscore the need for careful patient selection and close monitoring and support the use of teclistamab only in experienced centers with established multidisciplinary teams that integrate expertise in [autoimmune disease] with hematology-driven management of immune effector toxicities,” the authors wrote.

SOURCE

The study was led by Fredrik N. Albach, Elpida Phithak, and Robert Biesen, Charité-Universitätsmedizin Berlin, Berlin, Germany. It was published online on June 19, 2026, in Annals of the Rheumatic Diseases.

LIMITATIONS

The analysis was retrospective and based on individual treatment attempts outside a prospective clinical trial protocol. A comparator group was lacking, and this may have led to an overestimation of treatment effects. The duration of the disease and follow-up varied, and there was no standardization of clinical, serologic, and B-cell assessments across different centers.

DISCLOSURES

One author reported receiving support from the Horizon 2020 Framework Programme. Another author reported receiving support from the Else Kröner-Fresenius Stiftung through an Else Kröner Excellence Fellowship and from the Deutsche Gesellschaft für Rheumatologie und Klinische Immunologie through a Forschungsinitiative 2025 grant. Several authors reported receiving speaking and lecture fees and/or travel reimbursement and having other ties that include board membership with pharmaceutical and biopharmaceutical companies.

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