Successful autologous CD19 CAR T cell therapy following severe lupus flare during immunosuppressive washout in refractory lupus nephritis
Jonathan M. Gerber, Ehsan Dehdashtian, Guangnan Hu, Cara Gregoire, Dominic Borie, Poorva Bindal, Jan Černý, Abdallah Sassine Geara, G. Schett, Roberto Caricchio
Abstract
OBJECTIVE: To evaluate the safety and efficacy of CD19 chimeric antigen receptor (CAR) T cell therapy in a patient with refractory lupus nephritis who experienced severe disease flare during immunosuppressive washout, and to assess whether pulse corticosteroid intervention affects CAR T cell therapeutic outcomes. METHODS: We report a single case of a 22-year-old woman with SLE and lupus podocytopathy refractory to multiple therapies including rituximab, belimumab and obinutuzumab. The patient was treated under single-patient IND (#30146) with autologous CD19 CAR T cells (KYV-101). During the preinfusion washout period, she developed severe lupus flare requiring pulse intravenous methylprednisolone. Clinical outcomes, CAR T cell expansion, B cell depletion and laboratory parameters were monitored before and after therapy. RESULTS: Despite experiencing severe lupus flare (fever, rash, arthritis, anti-dsDNA elevation, hypocomplementaemia) during washout, pulse methylprednisolone (250 mg intravenous, rapidly tapered) successfully controlled symptoms without compromising subsequent CAR T cell expansion (peak 15.5 cells/µL on day 7). The patient achieved sustained clinical remission with SLE Disease Activity Index Score decreasing from 17 prior to leukapheresis to 4 by week 17. At 12 months postinfusion, she remained in drug-free remission with stable kidney function and had returned to full-time work. CONCLUSION: This case report illustrates that targeted pulse corticosteroids during CAR T cell therapy washout can effectively manage severe lupus flares without impairing therapeutic efficacy.