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.