5 years since Patient ID001: Progress on CAR-T Therapy in RMD Save

Efficacy of CAR-T therapy in a patient with severe refractory SLE was first published in 2021. Since then, there have been a plethora of preliminary results or data from early, non-controlled studies presented at EULAR and ACR conferences. Five years on, are we closer to licensing of the first CAR-T therapy in rheumatic and musculoskeletal diseases (RMD)? 

At EULAR 2026 Congress, London, data pertaining to rapid advances in cellular therapies across RMDs (RA, SLE, SSc, IIM, SjD and IgG4-RD) were presented. Several studies demonstrated novel strategies to optimise CAR-T and with encouraging efficacy signals, but also revealing important challenges related to durability, safety, accessibility, and long-term monitoring.

1. Expanding CAR-T targets. In (OP0311), this multicentre study in China reported short-term sustained remission by 6 months in 11 patients with severe refractory SSc including diffuse skin fibrosis and interstitial lung disease treated with dual-target CD19/BCMA CAR-T therapy. The findings suggest that targeting multiple immune pathways simultaneously may provide deeper depletion and more durable disease control than single-target approaches.

2. Improving CAR-T manufacturing time. Rapcabtagene Autoleucel (Rap-cel) reduces the manufacturing time from the traditional 7-14 days to about 2 days using a platform which avoids the need for prolonged ex vivo cell expansion. Preliminary data (OP077) reported early efficacy and no major safety signal in 6 patients with severe refractory SSc and 6 with IIM. Phase 2 open label RCT comparing Rap-cel with a comparator of investigator’s choice (Tacrolimus, MTX, MMF, Cyclophosphamide or Rituximab) is underway. 

3. Improving scalability. FT819 is an allogeneic, off-the-shelf anti-CD19 CAR-T therapy derived from a clonal master induced pluripotent stem cell (iPSC) bank. It required reduced or no preconditioning and supporting same-day discharge for patients. In Phase 1 study involving 13 patients with severe refractory SLE (with or without LN), efficacy was maintained up to 24 months. If preconditioning is required, the data favoured bendamustine over cyclophosphamide (POS0079). 

Notwithstanding the advances above, anecdotally patients with RMD may relapse after a course of CAR-T despite the “immune reset” campaign. “Immune dimming” has been introduced at this conference particularly since these patients are already severe and refractory to various immunosuppressive therapies. In the largest case series of 50 patients with SLE, SSc and IIM treated with Zorpo-cel autologous CD19 CAR-T therapy, relapses occurred in 12% of patients [SLE=1/28; SSc=2/14, IIM=3/8]. These relapses are major e.g. new transverse myelitis in SLE, progressive skin thickening and digital ulcerations in SSc and worsening ILD in IIM particularly anti-synthetase syndrome phenotype. Re-infusion of CAR-T failed to attenuate response. 3 patients were escalated to BCMA CAR-T while 2 received BCMA T cell engagers which all responded (OP076). A question arises whether BCMA should be targeted at the first place instead of CD19. 

Collectively, data presented at EULAR 2026 reinforce the transformative potential of CAR-T cell therapy in severe refractory RMDs. Major strengths across the studies include high remission rates, deep B-cell depletion, expansion into multiple disease indications, and development of more accessible off-the-shelf platforms. However, important limitations remain, including small sample sizes, early-stage clinical development, uncertain long-term safety, relapse management challenges, and the substantial economic and logistical barriers associated with cellular therapies. Larger studies with longer follow-up will be essential to determine whether CAR-T therapy can become a standard treatment option for refractory RMDs.