CD19 CAR T Shows Early Remission in Treatment-Refractory RA

Four of 6 patients with highly treatment-refractory rheumatoid arthritis (RA) achieved remission by week 36 after receiving a single infusion of CD19-directed chimeric antigen receptor (CAR) T-cell therapy in the phase 1 COMPARE trial. The small, open-label study met its primary safety endpoint, with investigators also reporting substantial reductions in disease-associated autoantibodies.¹

Fredrik Albach, MD, of the Department of Rheumatology and Clinical Immunology at Charité University Medicine Berlin, and colleagues are presenting the findings at the American College of Rheumatology (ACR) Convergence 2026 in Orlando, Florida. The results provide preliminary evidence of clinical activity in patients whose disease remained active despite multiple biologic and targeted therapies.¹,²

COMPARE Evaluates CD19 CAR T in Refractory RA

The phase 1 portion of the prospective, open-label phase 1/2 COMPARE trial enrolled 6 patients with active, anti-citrullinated protein antibody (ACPA)-positive RA. Participants had a median disease duration of 9.6 years and a median baseline Disease Activity Score in 28 Joints using C-reactive protein (DAS28-CRP) of 5.5.¹

Patients had received a median of 6.5 prior biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), including rituximab in 4 patients. Each participant received fludarabine/cyclophosphamide lymphodepletion followed by a single infusion of autologous CD19-directed CAR T cells, mivocabtagene autoleucel.¹

The primary endpoint was safety, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and adverse events. Secondary and exploratory endpoints included clinical activity, CAR T-cell expansion, B-cell depletion and reconstitution, autoantibody dynamics, and longitudinal immune profiling. Median follow-up was 36 weeks (range, 36-52).¹

Four Patients Achieve Remission by Week 36

All 6 participants demonstrated clinical improvement after discontinuation of immunosuppressive therapies. By week 36, 4 had achieved DAS28-CRP remission and an American College of Rheumatology 70% improvement response (ACR70).¹,²

The trial met its primary safety endpoint. CRS occurred at grade 1 in 4 patients and grade 2 in 2 patients. No ICANS was reported, although 1 participant experienced a transient dose-limiting elevation in liver enzymes.¹,²

Investigators observed CAR T-cell expansion and profound B-cell depletion in blood and tissue compartments. This was accompanied by a 94% reduction in antibodies against mutated citrullinated vimentin (MCV-ACPA), with seroconversion reported in 5 patients, and an 89% reduction in rheumatoid factor immunoglobulin M (RF IgM), with seroconversion reported in 4 patients.¹

Repopulating B cells predominantly exhibited a naïve or transitional phenotype without cyclic citrullinated peptide reactivity.¹

Responses were not uniform. Two patients experienced disease flares during follow-up, including 1 following glucocorticoid withdrawal in the setting of ongoing disease activity and another after 10 months of prior remission.¹

“These early Phase 1 results demonstrate that CD19 CAR T-cell therapy was feasible and met the study’s primary safety endpoint in this small cohort, while showing clinically meaningful activity,” Albach said in an ACR statement.²

The findings remain preliminary given the 6-patient sample, lack of a comparator group, and limited follow-up. The results do not establish comparative efficacy, long-term remission durability, or the safety profile of CD19 CAR T-cell therapy in a broader RA population.

Separate Lupus Study Examines Patient Priorities for CAR T

A separate ACR 2026 study examined how patients with severe systemic lupus erythematosus (SLE) evaluate the potential benefits and risks of allogeneic CAR T-cell therapy.³

Conducted through a collaboration between the Lupus Foundation of America and Fate Therapeutics, the qualitative study involved 5 adults with active, severe SLE. All participants identified as Black/African American women, including 1 who also identified as Hispanic. The study evaluated patient preferences regarding FT819, an investigational, induced pluripotent stem cell-derived, off-the-shelf CAR T-cell therapy.³

Participants reported taking 2-4 SLE-specific medications and 6-17 additional medications, with some receiving care from as many as 12 physicians. Safety ranked as the highest treatment priority for 4 of 5 participants, while speed of clinical effect consistently ranked lowest.²,³

Duration of benefit also influenced treatment preferences. Participants generally considered 1 year insufficient, identified 2 years as the minimum acceptable duration, and preferred benefit lasting at least 5 years. All 5 expressed a preference for the allogeneic approach over autologous CAR T-cell therapy, citing anticipated advantages in availability, hospitalization, conditioning intensity, and product consistency.²,³

However, interest remained conditional on safety, specialist care, financial support, and other treatment-related considerations. These preferences were reported by a small, selected focus group and cannot establish the clinical superiority or broader acceptability of allogeneic CAR T-cell therapy in SLE.

The COMPARE results and lupus patient-perspectives findings address different questions in CAR T-cell development. Together, they highlight the need for larger controlled clinical studies and further research into patient priorities as these investigational therapies advance.

References

1. Albach F, Rehm M, Hütter-Krönke ML, et al. CD19 CAR T-cell therapy in highly treatment-refractory rheumatoid arthritis: phase 1 results from the COMPARE trial. Arthritis Rheumatol. 2026;78(suppl 9). Abstract 1902. ACR abstract. Accessed November 8, 2026.

2. American College of Rheumatology. New ACR Convergence 2026 data highlight both clinical promise and patient priorities for CAR T-cell therapy in severe autoimmune disease. Published November 7, 2026. Accessed November 8, 2026. ACR press release.

3. Buie J, Agyemang S, Henry A, et al. Patient perspectives on allogeneic CAR T cell therapy in systemic lupus erythematosus: findings from a focus group study (part 3). Arthritis Rheumatol. 2026;78(suppl 9). Abstract 1539. ACR abstract. Accessed November 8, 2026.