Good news, but a very small sample size! Impressive!
"Immunotherapies such as CAR T-cell therapy are used primarily to treat cancer. In the future, these patient-specific therapies, manufactured from patients’ own immune cells, could also help cure autoimmune diseases.
Six patients with particularly severe rheumatoid arthritis have now received this treatment at Charité – Universitätsmedizin Berlin. In the journal Nature Medicine*, the researchers report the results from the world’s first clinical trial of its kind: Disease activity decreased substantially in all participants. By the end of the observation period, three of the patients no longer required any medication for rheumatoid arthritis. ...
Currently available treatments can usually keep the inflammation under control, but do not cure the disease. Patients therefore require lifelong medication ...
For the world’s first clinical trial to evaluate the safety and efficacy of a CD19 CAR T-cell therapy in rheumatoid arthritis, the research team ... initially enrolled six patients with particularly severe disease. The three women and three men, aged 31 to 69, had received up to eight targeted or biologic therapies over the previous ten years, none of which had been sufficiently effective. ...
For the researchers, the results from the first part of the COMPARE trial are highly encouraging: “Disease activity decreased markedly in all six patients. During follow-up of up to one year, three patients were in sustained remission without any medication for rheumatoid arthritis,” ..."
From the abstract:
"Chimeric antigen receptor (CAR) T cell-mediated B cell depletion has demonstrated efficacy in several autoimmune diseases.
Here we report clinical and molecular data obtained during the nonrandomized phase 1 part of the phase 1/2 COMPARE trial, evaluating safety and efficacy of mivocabtagene autoleucel (miv-cel), an autologous fully human CD19 CAR T cell therapy, in rheumatoid arthritis (RA).
Six patients (three men, three women) with severe, treatment-refractory, anti-citrullinated protein antibody (ACPA)-positive RA received a single infusion of miv-cel after stopping all disease-modifying antirheumatic drug treatments and after standard lymphodepletion therapy.
Patients were followed for 36–52 weeks for safety and efficacy.
Primary endpoints were the incidence and severity of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) and adverse events (AEs) within the first 4 weeks after treatment.
Secondary and explorative endpoints assessed clinical efficacy and cellular and humoral immune responses.
CRS occurred in all patients and was limited to grade 1 and 2 events. No ICANSs or serious AEs occurred; one dose-limiting toxicity was recorded (grade 3 transaminase elevation, resolved without sequelae).
The primary endpoint was met with acceptable safety findings, allowing advancement to phase 2.
CAR T cell therapy resulted in depletion of CD19+ B cells across blood and tissue, coinciding with a continuous decline of autoantibodies with seroconversion in four of the six patients for ACPAs against mutated citrullinated vimentin and five of six for rheumatoid factor immunoglobulin M.
Despite cessation of immunosuppressive treatments, disease activity improved in all patients (median 34% DAS28-CRP reduction at the latest follow-up with DAS28-CRP remission and American College of Rheumatology 70% response in 3 of 6 patients).
CD19 CAR T cells showed acceptable short-term tolerability in patients with treatment-refractory RA, justifying further evaluation. ..."
Charité study demonstrates efficacy of CD19 CAR T cells in first patients (original news release)
CD19 CAR T cell therapy for treatment-refractory seropositive rheumatoid arthritis: a phase 1 trial (no public access)
Patients own immune cells genetically modified in the laboratory, track down the disease driving B cells, even deep within tissues. Inflammatory foci such as those seen here around the knee joints of a study participant (magenta) are no longer detectable even several months after CD19-CAR T-cell therapy (right in the PET-MRI image). Swelling and pain have subsided, with improved mobility.
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