CAR-T Therapy Shows Durable Benefits in Myasthenia Gravis

Mivocabtagene autoleucel (miv-cel), an autologous CD19 chimeric antigen receptor (CAR)-T cell therapy, showed benefits lasting 6 months or longer for generalized myasthenia gravis patients in the phase II portion of the KYSA-6 trial.

At 24 weeks, all seven trial participants sustained clinically meaningful improvements in Myasthenia Gravis Activities of Daily Living (MG-ADL) and in Quantitative Myasthenia Gravis (QMG) scores, with mean reductions of -8.3 points and -11.7 points from baseline, respectively, reported Srikanth Muppidi, MD, of Stanford Health Care in Palo Alto, California, at the 2026 American Association of Neuromuscular and Electrodiagnostic Medicine meeting in Orlando.

MG-ADL scores can range from 0-24 and QMG scores can range from 0-39, with higher values in both scales indicating more severe disease or greater impairment.

All participants remained free of immunotherapies at 24 weeks, including nonsteroidal immunosuppressive therapies and high-dose steroids, and did not use neonatal Fc receptor (FcRn) or complement inhibitors.

No cases of severe cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) emerged. CRS was low-grade and manageable in all patients, Muppidi said.

One patient had transient grade 4 neutropenia that resolved within 10 days post-infusion. Another experienced grade 4 neutropenia that was successfully managed with granulocyte-colony stimulating factor (G-CSF) and resolved within 2 months after the infusion.

B cells play a role in myasthenia gravis; the disease is characterized by the presence of autoantibodies, often anti-acetylcholine receptor (AChR) or anti-muscle-specific kinase (MuSK) antibodies.

Miv-cel is a fully human, autologous, CD19-targeting CAR T-cell therapy that incorporates CD28 co-stimulation. “It has been used in more than 100 patients across multiple indications,” Muppidi said. “There have been three patients in Germany previously treated who had a durable benefit over 24 months. The side effect profiles were very predictable and well tolerated.”

The open-label, single-arm, phase II portion of the KYSA-6 trial enrolled seven generalized myasthenia gravis patients who either failed two immunosuppressive agents, or failed one and required treatment. All patients had lymphodepletion followed by a single CAR-T infusion.

Mean baseline age was 46 years and six participants were women. Five patients were AChR-positive and two were MuSK-positive. One had a history of thymoma.

At baseline, participants had a mean MG-ADL score of 11, a mean QMG score of 16.9, and a disease duration of 6.5 years. “These patients had fairly high symptom burden,” Muppidi pointed out.

“What is … impressive for me is that these patients could come off their prior immunotherapy, including high-dose steroids, non-steroidal immune agents, or prior FcRn or complement therapy for 24 weeks,” he added.

As of data cutoff in June 2026, follow-up extended up to 1.5 years in five patients, 9 months in one patient, and 6 months in another patient. Median follow-up was 13.9 months.

Clinically meaningful improvements in MG-ADL, QMG, and Myasthenia Gravis Composite scores were maintained through 1 year or longer in five patients who reached this time point, Muppidi said. At last follow-up, 57% of participants had minimal symptom expression, defined as an MG-ADL score of 0 or 1.

Six patients remained off immunosuppressants at last follow-up. In three patients who had antibody levels assessed before the study, there was evidence of immune reset and preserved humoral immunity.

The randomized phase III portion of the KYSA-6 trial is ongoing; it compares miv-cel against standard care with MG-ADL and QMG scores as co-primary endpoints. Miv-cel also is being studied in stiff-person syndrome, where it was shown to help patients regain mobility.