Background/Purpose: The goals of treatment for idiopathic inflammatory myopathy (IIM) are to eliminate or reduce inflammation, restore muscle performance, reduce morbidity, and improve a patient’s quality of life. Therapies providing durable meaningful clinical responses without requiring chronic administration are lacking. Rese-cel (formerly CABA-201), is a fully human, autologous 4-1BB CD19-CAR T cell therapy, designed to deeply and transiently deplete CD19 positive cells following a weight-based, single infusion with the potential to enable an “immune system reset” with durable responses. RESET-MyositisTM (NCT06154252) is an ongoing Phase 1/2 trial evaluating rese-cel in 3 independent cohorts of adults with dermatomyositis [DM], antisynthetase syndrome [ASyS] and immune mediated necrotizing myopathy [IMNM].

Methods: Patients were 18 to 75 years with refractory IIM per 2017 ACR/EULAR classification criteria, with myositis specific autoantibody (MSA), manual muscle test ≤142, at least moderate disease activity on 2 or more core set measures (CSMs). A weight-based infusion of 1×106 CAR T cells/kg was given following preconditioning with fludarabine and cyclophosphamide. All non-glucocorticoid (GC) IM agents were discontinued by Day –5. Adverse events, use of IM medications and efficacy measurements to calculate the TIS were collected. CAR T cells and B cells were profiled in peripheral blood pre- and post-infusion by digital PCR and flow cytometry, respectively. Serum cytokines were measured using the mesoscale discovery platform.

Results: As of 31 March 2025, 6 patients have been infused with rese-cel and have at least 1 month of follow-up (Table 1). Additional patients were recently infused and are in early follow-up.Rese-cel was well-tolerated in all 6 patients with Grade 1 cytokine release syndrome (CRS) in 3 of 6 patients, and no Grade 2 or higher CRS, dose-limiting toxicity or immune effector cell-associated neurotoxicity syndrome (ICANS). IMNM-2 with multiple risk factors, experienced a pulmonary embolism (PE) on Day 38, which was assessed as unrelated to rese-cel. Five out of 6 patients achieved a drug-free clinical response on TIS (Table 2).Rese-cel expanded rapidly in all patients and peaked between days 8 and 14 after infusion. Serum IFNγ levels increased post-infusion and peaked prior to rese-cel peak expansion. Rese-cel contracted quickly and was undetectable peripherally within the first 8 weeks in most patients. B cells (CD19+CD20+) were rapidly reduced to undetectable levels by 14 days and through the first month post rese-cel infusion in all patients. B cell reconstitution occurred as early as 8 weeks after infusion in 4 patients and 12 weeks in 1 patient. Reemergent B cells had predominantly transitional naïve phenotype (CD19+CD20+CD38++CD24++).

Conclusion: Data from IIM patients infused with rese-cel show early drug-free clinical responses in most patients and acceptable safety in the setting of rese-cel expansion and peripheral B cell depletion. DM & ASyS patients achieved a higher threshold of response than IMNM which is not unexpected. These initial data suggest the potential for rese-cel to reset the immune system, allowing patients to achieve meaningful drug-free clinical responses.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/reset-myositis-clinical-trial-evaluating-rese-cel-resecabtagene-autoleucel-a-fully-human-autologous-4-1bb-cd19-car-t-cell-therapy-in-idiopathic-inflammatory-myopathies/