Findings from the phase 1/2 RESET-MG trial, presented at AANEM 2026, showed that 10 of 13 patients with refractory generalized myasthenia gravis had clinically meaningful MG-ADL improvements after a single infusion of rese-cel.
A single infusion of resecabtagene autoleucel (rese-cel; Cabaletta Bio), an investigational, fully human, autologous 4-1BB CD19-directed chimeric antigen receptor (CAR) T-cell therapy, produced clinically meaningful improvements in a phase 1/2 trial of patients with refractory generalized myasthenia gravis (gMG). These patients were off immunomodulatory therapies, and the therapy was generally well tolerated, according to data from the RESET-MG(NCT06359041), an early-stage study.1
These findings were recently presented by
RESET-MG enrolled adults aged 18 to 70 years with Myasthenia Gravis Foundation of America class II to IV gMG and an MG Activities of Daily Living (MG-ADL) score of 6 or greater despite at least 2 prior or current treatments. Patients were enrolled in 2 cohorts: anti-acetylcholine receptor (AChR) antibody–positive and AChR antibody–negative. Nonglucocorticoid immunomodulatory agents were discontinued before standard preconditioning, and patients then received a single rese-cel infusion at 1 × 106 cells/kg. Investigators assessed adverse events, gMG medication use, disease activity, and translational end points.
For context, rese-cel is designed to deeply and transiently deplete CD19-positive B cells after a single weight-based infusion. The goal of the agent is an "immune reset" that could allow durable responses without ongoing gMG medications.1
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As of March 2026, 13 patients had received rese-cel (AChR-positive, n = 7; AChR-negative, n = 6), with follow-up ranging from 8 to 44 weeks. Low-grade cytokine release syndrome (CRS) occurred in 2 patients. Rese-cel expansion peaked and B cells were depleted by day 15 in all patients. Among patients with available data, B cells reconstituted in 7 of 13 at a median of 85 days (IQR, 56-111).
Ten patients had clinically meaningful MG-ADL improvements off immunomodulators: 5 in the AChR-positive cohort and 5 in the AChR-negative cohort. Nine of these patients were off or tapering glucocorticoids, and 1 continued glucocorticoids because of adrenal insufficiency. Among patients who did not receive rescue therapy, mean MG-ADL improvement from baseline was 7.4 points at week 12 (n = 11) and 9.8 points at week 24 (n = 4). According to the data presented at the 2026 AAN Annual Meeting, the remaining 3 patients received rescue therapy for insufficient response, 2 in the AChR-positive cohort received intravenous immunoglobulin, and 1 in the AChR-negative cohort received efgartigimod and intravenous immunoglobulin.2
The findings add to a growing body of evidence for CD19-directed CAR T-cell therapy in gMG. That evidence dates to a 2023 case report of a patient with severe, treatment-refractory AChR-positive gMG who improved after anti-CD19 CAR T-cell therapy.3
The inclusion of an AChR antibody–negative cohort is notable, given the more limited targeted treatment options for these patients. After the RESET-MG phase 1/2 data were first presented at AAN 2026, the FDA granted rese-cel regenerative medicine advanced therapy designation for gMG. Cabaletta has also announced plans to add dose exploration of rese-cel without preconditioning to RESET-MG.4
These results should be interpreted cautiously. The study is small, open label, and single arm, with no control group, and follow-up remains short. Only 4 patients contributed data at week 24, which limits conclusions about durability. Responses measured by MG-ADL, a patient-reported scale, may be subject to expectation bias in an unblinded setting.
Nearly half of patients had not yet shown B-cell reconstitution, and longer follow-up will be needed to determine whether responses persist after B cells return. The preconditioning regimen also carries its own risks and practical burdens. Larger controlled studies will be needed to define efficacy, long-term safety, and the potential role of CAR T-cell therapy relative to established targeted gMG therapies.
