ABS0364 SAFETY AND EFFICACY OF T CELL ENGAGER THERAPY IN PATIENTS WITH REFRACTORY AUTOIMMUNE DISEASE

Abstract

Background:

T cell engagers (TCEs) redirect T cells for targeted cytotoxicity and are emerging as promising therapeutic strategy to deplete B cells in autoimmune disease (AID). Recent data demonstrate the safety and short-term clinical efficacy of CD19 and BCMA targeted T cell engagers in various AID, yet patient numbers and length of follow-up remain limited [1–3].

Objectives:

Here we present a current analysis of the safety and clinical efficacy from 24 patients with various autoimmune diseases treated with TCEs.

Methods:

A total of 24 patients with multi-drug-resistant autoimmune diseases (AIDs) received TCE therapy as inpatients in our center in a compassionate use program. 14 patients with rheumatoid arthritis (RA) were treated with the CD19xCD3 TCE blinatumomab, while 10 patients (systemic sclerosis (SSc), N=3, idiopathic inflammatory myositis (IIM) N=2, IgG4-related disease (IgG4-RD) N=2, primary Sjoegren's-Syndrome (SjS) N=1, Graves disease (GD) N=1,) and RA N=1) were treated with the plasma cells targeting BCMAxCD3 TCE teclistamab. RA patients received 2–3 cycles of low dose blinatumomab therapy as 96-hour continuous intravenous infusion. The cumulative dose of Blinatumomab ranged from 77 µg to 189 µg. Teclistamab was administered as subcutaneous injection using the standard step-up dose (d1: 0.06 mg/Kg; d3: 0.3 mg/Kg; d5: 1.5 mg/Kg). A maintenance dose of 1.5 mg/Kg was administered after 4 weeks. Adverse events such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) and immune effector cell–associated hematotoxicity syndrome (ICAHTS) were recorded and monitored after the therapy. Clinical efficacy was assessed using the disease-specific combined scores (DAS 28; ESSDAI; mRSS; CDASI, MMT8) and the visual analog scale (VAS).

Results:

Treatment with both oth TCEs was well tolerated. No cases of ICANS and ICAHTS were recorded. Low-grade CRS (grade 1-2) was observed in 3 of 14 patients treated with blinatumomab and in 8 of 10 patients treated with teclistamab. Mild infections occurred in 4 of 14 of patients treated with blinatumomab and in all patients treated with Teclistamab. Three severe infections were observed after teclistamab: one viral gastroenteritis with dehydration, which resolved upon symptomatic management and two bacterial infections (Clostridium difficile infection and urinary tract infection), which resolved upon intravenous antibiotic treatment. All patients showed initial clinical and serological response. In RA patients treated with blinatumomab, the median number of tender joints decreased from 9 [range: 2–39] to 1.5 [range: 0–5] and the number of swollen joints decreased from 8 [range: 1–35] to 1 [range: 0–6] VAS improved from 70 [range: 40–90] to 20 [range: 0–60]. DAS28-CRP decreased from 5.13 to 2.6, leading to DAS28-CRP remission in 9/14 patients at month 3. Two patients stayed in drug-free remission (3 and 6 months). Over time, 12 of 14 patients treated with blinatumomab relapsed, after a median durability of response of 5.5 [2–18] months. In patients treated with teclistamab, mRSS decreased in SSc patients from a median value of 34 [range: 10–39] to 16 [range: 9–24], ESSDAI decreased in the SjS patient from 34 to 12 at 3-month follow up. DAS 28 decreased in the RA patient from 5.59 to 2.1, CDASI improved in the IIM patient from 22 to 5 and MMT8 from 138 to 150. Also endocrine opthalmopathy in Graves Disease and organ manifestations in IgG4 syndrome improved. IgG4 levels and most disease specific autoantibodies significantly decreased (ANA, Ro-52, Ro-60, SS-B/La, Th/To, PL7) or even seroconverted (RF, ACPA, MCV, PM-Scl75, PM-Scl100, Scl70, MDA5, M2, Mi2a and TRAK). 8/10 patients are currently in drug-free remission, with a median durability of response of 6 [3–11] months. 2/10 patients treated with Teclistamab relapsed after a median of 6 [5-7] months.

Conclusion:

Together, these results substantiate the feasibility of TCE treatment of to autoimmune disease. Most notable adverse events are low grade cytokine release syndrome and infections. Short term efficacy is high even in a refractory patient population, however relapses occur. Future work is required to identify the optimum dosing schedule for different autoimmune diseases and to test in how many patients lasting drug remission might be achievable.

REFERENCES:

[1] Bucci, Laura et al. "Bispecific T cell engager therapy for refractory rheumatoid arthritis." Nature medicine vol. 30,6 (2024): 1593-1601. doi:10.1038/s41591-024-02964-1. [2] Hagen, Melanie et al. "BCMA-Targeted T-Cell–Engager Therapy for Autoimmune Disease." N Engl J Med 2024;391:867-869. DOI: 10.1056/NEJMc2408786. [3] Alexander, Tobias et al. "Teclistamab-Induced Remission in Refractory Systemic Lupus Erythematosus." The New England journal of medicine vol. 391,9 (2024): 864-866. doi:10.1056/NEJMc2407150.

Acknowledgements:

NIL.

Disclosure of Interests:

Laura Bucci: None declared, Sebastian Boeltz: None declared, Melanie Hagen: None declared, Danae-Mona Nöthling: None declared, Tobias Rothe: None declared, Carlo Tur: None declared, Andreas Wirsching: None declared, Janina Auth: None declared, Jochen Wacker: None declared, Markus Eckstein: None declared, Stefano Alivernini: None declared, Aline Bozec: None declared, Christina Bergmann: None declared, Maria Antonietta D'Agostino: None declared, Maria Gabriella Raimondo: None declared, Georg Schett BMS, Cabaletta, Johnson & Johnson, Kyverna, Novartis, UCB, Ricardo Grieshaber-Bouyer Bristol-Myers Squibb, Cullinan, Janssen, Lilly, Novartis, Astra Zeneca, Kyverna. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.