A German man has achieved sustained, drug-free remission of RA disease activity for the first time in two decades after receiving CD19 CAR T cell therapy.
“You got a fast CAR (T cell therapy)… Is it fast enough so we can beat RA?” – Tracy Chapman.
A new case report, published last month in EULAR Rheumatology Open, details a ‘rapid and profound’ response to CAR T cell therapy in an elderly patient with difficult-to-treat rheumatoid arthritis.
The patient, a 70-year-old man, had been living with RA for 20 years. He had no record of achieving stable disease remission prior to the CD19 CAR T cell therapy, despite being treated with glucocorticoids, various DMARDs (methotrexate, leflunomide and sulfasalazine) and a range of targeted therapies (adalimumab, etanercept, certolizumab, tocilizumab, abatacept, rituximab, sarilumab and golimumab) at various timepoints over the previous two decades.
However, all treatments – apart from methotrexate and leflunomide – had been ceased after being trialled due to insufficient efficacy.
After undergoing immunosuppressive treatment, leukapheresis and lymphodepletion, the patient underwent three days of CD19 CAR T cell therapy (KYV-101, Kyverna Therapeutics).
There was a significant increase in CD19 CAR T cell levels that peaked at day 10, before declining over the next three months. Peripheral CD19+ B cell levels also rapidly fell, with B cell depletion and reconstitution demonstrated at 12- and 35-weeks post-treatment, respectively.
CAR T cell therapy led to sustained, drug-free remission of disease activity, with the disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR) decreasing from 5.46 at baseline to 1.74 at month 8. There was also a significant reduction in inflammation, as measured by whole-body high-resolution metabolic imaging, musculoskeletal ultrasound and fluorescence optical imaging.
The patient also displayed a significant improvement in fatigue, seen through an increase in their Functional Assessment of Chronic Illness Therapy – Fatigue Scale scores: 31 prior to therapy to 46 at month 8 (range 0-52, where higher scores indicate better quality of life).
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Although the patient experienced cytokine release syndrome in the initial post-infusion stage – which resolved after being treated with tocilizumab and dexamethasone – there were no reports of immune effector cell-associated neurotoxicity syndrome, infections or bone marrow toxicity at any point during the eight-month follow-up period.
“These findings demonstrate clinical efficacy of CD19 CAR T cell therapy in D2T RA with a favourable safety profile,” the researchers concluded. “Consistent with previous reports, this case further substantiates the potential of CD 19 CAR T cell therapy in D2T RA.”
“Ongoing clinical trials… comparing CD19 CAR T cell therapy with rituximab, are expected to provide further important insights into long-term efficacy and safety. These results may ultimately clarify whether CAR T cell therapy can initiate a paradigm shift in RA by enabling a durable reset of autoimmunity and sustained drug-free remission.”
