1198: Induction of stable, GC-free remission in patients with severe, therapy-refractory anti-synthetase syndrome after using the bispecific CD19xCD3 T cell engager blinatumomab
Background/Purpose: Treatment of anti-synthetase syndrome (ASyS) presents clinical challenges: myositis can lead to permanent disability and severe organ involvement is life-threatening. Methods: We treated three patients with multidrug-resistant severe anti-Jo-1 positive ASyS with blinatumomab 143µg and added rituximab (RTX) 1000mg for maintenance therapy. Patient 1, 67-year-old female, had reoccurring myositis and new interstitial lung disease (ILD). Patient 2, 36-year-old male, suffered from progressive ILD and myocarditis. Patient 3, 47-year-old male, had debilitating myositis. All patients were unresponsive to at least three immunosuppressants including rituximab. Results: Blinatumomab induced complete depletion of CD19+ B cells in circulation and muscle tissue (Figure 2) and profound decreases in anti-Jo-1 titers. Blinatumomab induced glucocorticoid-free remission with normalization of muscle enzymes, improvement of muscle strength (Figure 1) in all patients.
Patient 1 showed an increase in CD19+ B cells and recurrence of myositis 4 months after blinatumomab. We re-started blinatumomab plus RTX and reinduced clinical remission followed by maintenance therapy with RTX (follow-up six months).
Patient 2 showed ongoing remission of myositis and improvement of ILD for six months after blinatumomab and repeated RTX.
Patient 3 demonstrated ongoing remission for 6 months after blinatumomab and RTX.
Adverse events: cytokine release syndrome (CRS) grade 3 (same day recovery) and respiratory infection in patient 3. No neurotoxicity occurred. Conclusion: This is the first report on treating patients with severe, treatment-refractory ASyS with blinatumomab. When followed by RTX, glucocorticoid-free remission remained stable for up to 10 months follow-up. Combining blinatumomab with RTX may offer potential in treatment-refractory ASyS patients.
