Safety and efficacy of blinatumomab in the treatment of refractory systemic sclerosis: a case series.

Abstract

This study aims to evaluate the safety, biological activity, and exploratory clinical effects of CD19-directed T-cell engagement with blinatumomab in patients with severe, treatment-refractory antitopoisomerase I-positive systemic sclerosis (SSc). We conducted an exploratory case series of 5 patients with refractory SSc who received a 14-day continuous intravenous infusion of blinatumomab (9 µg/d for 7 days, escalated to 28 µg/d for 7 days) in 2 tertiary hospitals. Safety assessments included cytokine release syndrome (CRS), neurotoxicity, infections, and serum immunoglobulin levels. Exploratory efficacy outcomes comprised modified Rodnan skin score (mRSS), pulmonary function tests, and patient-reported outcomes. Immunologic endpoints included serial peripheral CD19⁺ B-cell counts, B-cell subset phenotyping, and a 6-gene type I interferon signature. Patients' follow-up was a median of 8 months (range: 6-12). Blinatumomab administration was generally well tolerated. Three patients experienced low-grade CRS (grade 1, n = 2; grade 2, n = 1), managed conservatively; no neurotoxicity or severe infections occurred. Rapid peripheral CD19⁺ B-cell depletion was achieved in all patients. B-cell repopulation occurred by 1 month in all but 1 patient and was dominated by naïve and transitional subsets. At 3 months, modest clinical improvements were observed, including a median mRSS change of -4 points (range: +1 to -8) from a baseline of 16 (range: 0-25) and a transient improvement in lung function and patient-reported outcomes. However, all patients experienced clinical relapse between months 3 and 6, leading to resumption of immunosuppressive therapy in most cases. CD19-directed T-cell engagement with blinatumomab induces rapid B-cell depletion and short-term clinical improvement in refractory SSc but lacks durability after a single treatment cycle.