Background/Purpose: Idiopathic inflammatory myopathies (IIMs) are systemic autoimmune diseases affecting muscles, skin, lungs, joints, and several other organs; many patients are refractory to available therapy, highlighting the need for novel treatments. BMS-986353 is an investigational CD19-directed autologous chimeric antigen receptor (CAR) T cell therapy being studied in autoimmune diseases. We present the first report on the tolerability and efficacy of BMS-986353 in patients with severe refractory IIMs from Breakfree-1 (NCT05869955).

Methods: Patients with IIM with severe muscle involvement (manual muscle test [MMT]-8 < 130) despite treatment with glucocorticoids and ≥2 immunosuppressants (ISTs) were treated with a single BMS-986353 infusion of 10×106 CAR T cells following lymphodepletion. All patients discontinued IIM-specific therapies and steroids (≥5 mg prednisone equivalent, except when directed for adrenal insufficiency) before lymphodepletion. Primary endpoint was safety.

Results: As of August 14, 2025, 13 patients were evaluable for safety. Before enrollment, patients received a median 6 (range 3–9) prior ISTs. Eleven patients were evaluable for efficacy (antisynthetase syndrome, n=3; DM, n=3; PM, n=2; immune-mediated necrotizing myopathy [IMNM], n=3), with median baseline MMT-8 score of 121 (range 72−133). Median follow-up was 87 days (range 4–375).Six of 13 (46.2%) patients developed low-grade (Gr) cytokine release syndrome (Gr 1, n=5; Gr 2, n=1; Table). One patient had immune effector cell-associated neurotoxicity syndrome (Gr 3) characterized by decreased level of consciousness and aphasia, which resolved in 3 days with dexamethasone. Two transient hematologic treatment-emergent adverse events of Gr ≥3 (neutropenia, n=1; anemia, n=1) were reported. There were no prolonged cytopenias (lasting >28 days) or treatment-emergent serious infections.

Of the 11 efficacy-evaluable patients, 7 (63.6%) achieved a major response and 3 (27.3%) a moderate response based on Myositis Response Criteria—Total Improvement Score (MRC-TIS). All 11 patients experienced a rapid and significant improvement in muscle strength; median increase in MMT-8 score from baseline was 22.0 points at day 85 (n=6) and 27 points at day 169 (n=3). One patient with IMNM with a >10-year disease duration and minimally elevated baseline creatine kinase had an improved MMT-8 without achieving ≥moderate MRC-TIS response (Figure 1). Ten of 11 efficacy-evaluable patients remained off IIM-directed therapy at last follow-up, with 1 patient empirically restarting IVIG for elevated creatine kinase despite improvement in MMT-8 score.

All patients had robust CAR T cell expansion and achieved complete peripheral blood B-cell depletion (Figure 2). IIM-related autoantibody levels decreased post-infusion.

Conclusion: Findings from Breakfree-1 demonstrate a manageable safety profile, robust CAR T cell expansion, complete B-cell depletion, and promising efficacy of BMS-986353 without IIM-directed therapies in >90% of patients with severe refractory IIMs.

Medical writing: Sameen Yousaf, PhD (Caudex, an IPG Health company), funded by BMS.

Table

Figure 1. MRC-TIS (A) and MMT-8 (B) following BMS-986353 infusion in efficacy-evaluable IIM population.

ASyS, antisynthetase syndrome; IMNM, immune-mediated necrotizing myopathy; M, month.

Figure 2. CAR transgene levels (A) and peripheral blood B cell depletion/reconstitution (B) in evaluable IIM population.

Transgene levels refer to the number of genetic copies of the engineered CAR construct present in a patient’s blood, as measured by droplet digital PCR.

CAR, chimeric antigen receptor; PT, pre-treatment.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/promising-early-outcomes-with-bms-986353-a-cd19-directed-chimeric-antigen-receptor-t-cell-therapy-in-severe-refractory-idiopathic-inflammatory-myopathies-safety-and-efficacy-findings-from-the-ongoin/