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&#3f3, idiopathic inflammatory myositis (IIM) N&#3f2, IgG4-related disease (IgG4-RD) N&#3f2, primary Sjogren’s-Syndrome (SjS) N&#3f1, Graves disease (GD) N&#3f1, RA N&#3f1]. 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.

Figure 1. Safety of blinatumomab and teclistamab in autoimmune disease. (A) Overview of adverse events during blinatumomab therapy. (B) Overview of adverse events during teclistamab therapy.

Figure 2. Durability of response. (A) Blinatumomab and (B) teclistamab treatment timeline.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/safety-and-efficacy-of-t-cell-engager-therapy-in-patients-with-refractory-autoimmune-disease/