Background/Purpose: T cell engagers (TCEs) are a promising therapeutic strategy to treat autoimmune diseases (AID). However, long-term data remain limited. Methods: Patients with treatment-refractory AID were treated with the CD19 TCE blinatumomab or the BCMA TCE teclistamab. Eligibility criteria for blinatumomab were (i) diagnosis of rheumatoid arthritis (RA), (ii) ACPA/RF positivity or B-cell infiltration of the synovium, (iii) DAS28-ESR >3.2 and (iv) failure of ≥ 3 bDMARDs/tsDMARDs. Eligibility criteria for teclistamab: (i) diagnosis of AID according to respective diagnostic criteria, (ii) presence of characteristic autoantibodies, (iii) active disease based on respective criteria and ascertained by three specialists and (iv) failure of ≥ 2 immunosuppressants. Results: 24 patients received TCE therapy. Most (18/24) had previously failed B cell depletion. 14 RA patients received blinatumomab (2–3 cycles, cumulative dose 77–189µg). 10 patients received teclistamab [systemic sclerosis (SSc), N=3, idiopathic inflammatory myositis (IIM) N=2, IgG4-related disease (IgG4-RD) N=2, primary Sjogren’s-Syndrome (SjS) N=1, Graves disease (GD) N=1, RA N=1]. Teclistamab was administered s.c. (d1: 0.06 mg/Kg; d3: 0.3 mg/Kg; d5: 1.5 mg/Kg, week 4: 1.5 mg/Kg). Treatment with TCEs was well tolerated (Fig. 1). No high-grade CRS and no ICANS occurred.
In patients treated with blinatumomab, low-grade (1-2) CRS was observed in 3/14 cases.
Transient hypogammaglobulinemia occurred in one patient. Mild infections occurred in 4 patients; no severe infections were observed. In patients treated with teclistamab, low-grade CRS occurred in 8/10 cases and resolved upon tocilizumab infusion. Hypogammaglobulinemia occurred in 9/10 patients and resolved after a median of 2 [range: 1-5] immunoglobulin infusions. 3 severe infections were observed, which fully resolved (viral gastroenteritis, Clostridium difficile infection, urinary tract infection). Mild upper respiratory tract infections occurred in 8/10 patients.
All patients showed initial clinical and serological response. In blinatumomab-treated RA patients, average DAS28-CRP decreased from 5.13 to 2.6, leading to DAS remission in 9/14 patients at month 3. After a median response to blinatumomab of 3.8 months, 13/14 patients progressed and required further therapy; one patient stayed in remission (Fig. 2).
In patients treated with teclistamab, disease specific autoantibodies seroconverted or markedly decreased. Serum IgG4 and CRP normalized and organ manifestations of IgG4-RD improved. At 3-month follow-up, mRSS decreased on average by 10, ESSDAI decreased from 34 to 12, CDASI improved from 22 to 5 and MMT8 increased from 138 to 150. DAS28 decreased from 5.59 to 2.1. Interstitial lung disease improved (median KCO of 45% to 53% at month-3 follow up). In the patient with GD, endocrine orbitopathy reverted.
6/10 patients treated with teclistamab maintained clinical response (median: 9 months), 3/10 patients progressed after a median of 5.2 months, one patient showed initial non-response (Fig. 2). Conclusion: Our data substantiate an overall favorable safety profile and clinical efficacy of TCEs, warranting further investigation as treatments in different AIDs.
