MIVOCABTAGENE AUTOLEUCEL, an autologous, fully human CD19-directed CAR-T cell therapy, proves promising in treatment-refractory rheumatoid arthritis, according to an oral abstract presented today at EULAR 2026, London, UK.
Fredrik Albach, Charité Universitätsmedizin, Berlin, Germany, presented results from Phase I of the prospective, open-label COMPARE trial,1 analysing responses in six patients with anti-citrullinated protein antibody (ACPA)-positive, treatment-refractory active rheumatoid arthritis.
Rheumatoid Arthritis
In general, the treatment was well tolerated, with cytokine release syndrome limited to mild-to-moderate events and no immune effector cell-associated neurotoxicity syndrome or unexpected toxicities reported.
CAR-T cells expanded rapidly and peaked within three weeks, followed by a gradual decline.
B cells were effectively depleted in blood and tissues.
There was also a marked decrease in autoantibodies, with a median reduction greater than 90% and sustained seroconversion to normal ACPA achieved in four patients.
All six patients experienced a decrease in disease activity, with a median 49% DAS28-CRP reduction.
Half achieved sustained remission in the absence of ongoing immunosuppressive therapy.
Systemic Sclerosis
Another team reported on the first multicentre experience of dual-target CAR-T in 11 patients with refractory systemic sclerosis.
All patients achieved rapid B-cell aplasia and skin thickness scores improved significantly from baseline, with 73% reaching low disease activity.
Functional disability, measured by HAQ-DI, decreased from 1.0 t 0.2 and both physician and patient global assessments fell.
Lung progression was also targeted, with evidence of stabilisation or improvement in lung volume and oxygen transfer.
Regression of interstitial changes in 80% of patients with baseline interstitial lung disease was confirmed by high-resolution computed tomography scans.
No flares occurred during follow-up.
One patient with overlap syndrome required retreatment but achieved remission after their second infusion.
Yajing Zhang, GoBroad Boren Hospital, Beijing, China, said: “Dual target CD19/BCMA CAR-T cell therapy induces profound and sustained clinical remission in refractory systemic sclerosis.
“By effectively targeting both skin fibrosis and lung progression, this immunological ‘reset’ strategy offers true curative potential, paving the way for Phase II trials to redefine the future management of this severe disease.”
Clinical Implications
Current therapies for rheumatoid arthritis rely on sustained immunosuppression rather than restoration of immune tolerance, with off-drug remission remaining rare.
Taken together, findings support the concept of an immunological reset in a significant proportion of patients across different rheumatic and musculoskeletal diseases.
Reference
1 Albach FN et al. CD19 CAR T-cell therapy in ACPA-positive, treatment-refractory, active rheumatoid arthritis – data from the Phase 1 of the prospective, interventional COMPARE trial. Presented at EULAR 2026; OP008. Ann Rheum Dis 2026;DOI:10.1136/annrheumdis-2026 eular.B.2103.
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