This phase 1, nonrandomized part of the COMPARE trial evaluated safety and tolerability of autologous fully human CD19 CAR T cell therapy, mivocabtagene autoleucel (miv-cel), in patients with severe, treatment-refractory, seropositive rheumatoid arthritis (RA). The predefined primary endpoints were the incidence and severity of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) and other adverse events (AEs) within the first 4 weeks after infusion.
All six enrolled patients developed CRS, but events were limited to grade 1 or grade 2. No ICANS events or serious adverse events were reported within the primary safety observation window. One dose-limiting toxicity (DLT) was recorded: a grade 3 transaminase elevation that resolved without sequelae. Overall, the primary safety endpoint was met with findings judged acceptable to proceed to phase 2.
Six patients (three men and three women) with severe, treatment-refractory RA and positive anti-citrullinated protein antibodies (ACPA) received the investigational therapy. All disease-modifying antirheumatic drug treatments were stopped prior to CAR T cell infusion. Patients underwent standard lymphodepletion before receiving a single intravenous infusion of autologous miv-cel. Follow-up was conducted for 36–52 weeks to monitor safety and efficacy.
Details on individual baseline disease duration, prior therapies, specific lymphodepletion regimen and exact CAR T cell dose levels were not reported in the previewed source content.
Clinical efficacy was assessed through standard RA disease activity measures and response criteria. Despite discontinuation of background immunosuppressive therapies, disease activity improved in all six patients over follow-up. At the latest follow-up time point reported, the median reduction in DAS28-CRP was 34% across the cohort.
Three of six patients reached DAS28-CRP remission and achieved an American College of Rheumatology 70% improvement (ACR70) response. The observed improvements occurred in the setting of profound B cell depletion (see immune response section) and a progressive decline in autoantibody levels.
Infusion of miv-cel produced depletion of CD19+ B cells in peripheral blood and affected tissue compartments. This cellular depletion coincided with a sustained decline in disease-associated autoantibodies.
Autoantibody changes included seroconversion for specific targets in several participants: four of six patients seroconverted for ACPAs directed against mutated citrullinated vimentin, and five of six patients seroconverted for rheumatoid factor of the IgM isotype. The source reports a continuous decline in autoantibody titers but does not provide detailed longitudinal titers, timing of seroconversion for each patient, or correlations between antibody decline and clinical indices beyond the cohort-level outcomes.
The adverse event profile during the primary observation period was characterized primarily by low-grade CRS in all patients (grade 1–2). No ICANS events were observed. The single DLT—grade 3 transaminase elevation—resolved without lasting harm. No serious adverse events were reported in the phase 1 cohort. These short-term tolerability data supported progression of the trial to phase 2.
The source does not report longer-term safety beyond 36–52 weeks in detail, nor does it report infection rates, hematologic toxicities other than the transaminase event, or detailed management approaches used for CRS in this cohort.
In this nonrandomized phase 1 cohort of the COMPARE trial, a single infusion of autologous CD19 CAR T cell therapy (mivocabtagene autoleucel, miv-cel) in six patients with severe, treatment-refractory, ACPA-positive RA produced consistent CD19+ B cell depletion, reductions in autoantibody levels with seroconversion in several patients, and clinical improvement despite cessation of disease-modifying therapies.
Safety findings during the first 4 weeks showed universal but low-grade CRS, no ICANS, and a single reversible grade 3 transaminase elevation as the only DLT. These results met the primary safety endpoint and were judged sufficient to advance the program to phase 2.
ClinicalTrials.gov identifier provided in the source: NCT06475495.
Limitations reported or not reported in the source: the previewed content does not include full patient-level data, detailed dosing or manufacturing information, longer-term safety beyond the 36–52 week follow-up window, or randomized efficacy comparisons. Those details will be necessary to fully interpret durability of response, safety profile over time, and potential selection criteria for broader clinical application.
Overall, the phase 1 data indicate that CD19-directed CAR T cell therapy with miv-cel has acceptable short-term tolerability in this small cohort of seropositive, treatment-refractory RA patients and produces biologic effects (B cell depletion and autoantibody decline) accompanied by clinical improvement, justifying further evaluation in phase 2.