Teclistamab induces rapid clinical response and deep tissue depletion in refractory systemic sclerosis—a case series

OBJECTIVES: This study aimed to evaluate clinical outcomes, serologic changes, and immunologic effects induced by the bispecific B cell Maturation Antigen (BCMA)x Cluster of Differentiation (CD)3 T-cell-engaging antibody teclistamab in systemic sclerosis (SSc). METHODS: Patients with severe and treatment-refractory SSc were treated with teclistamab as off-label therapy. Blood and tissue samples from skin and bone marrow were analysed with immunohistochemistry and flow cytometry, serum antibodies were quantified by enzyme-linked immunosorbent assay (ELISA). Clinical efficacy was assessed using the American College of Rheumatology Composite Response Index in Systemic Sclerosis (ACR-CRISS) responses, among others. RESULTS: Ten patients with SSc (70% female; median age 51 years [IQR: 7]) completed 1 cycle of teclistamab. Two patients with advanced SSc heart involvement died shortly after treatment initiation. B-cells and plasma cells were almost completely eliminated from bone marrow and skin, accompanied by a median reduction of 70.6% (IQR: 39%) in antitopoisomerase antibody titres, decreases in serum IgG, and vaccination titres. After a median follow-up of 3.75 months (IQR: 2.5 months), 71% and 43% of patients achieved revised ACR-CRISS 25 and 50 responses, respectively. Among patients with interstitial lung disease, radiographic and functional improvement was observed by week 12 with a median increase in forced vital capacity of 7% (IQR: 15%). Skin fibrosis similarly improved, with a median decrease in the modified Rodnan skin score of 35.9% (IQR: 17.9%), accompanied by corresponding reductions in fibroblast activation protein (FAP)-alpha-positive fibroblasts in skin biopsy specimens. CONCLUSIONS: Teclistamab induced deep tissue depletion of B-cells and plasma cells and rapid clinical and serological responses, with evidence for resolution of inflammation and potential modification of fibrotic processes. These data suggest the potential of BCMA-directed therapies to promote immune modulation and tissue remodelling.