Beyond Biologics: Emerging Cell-Based and Targeted Therapies in Rheumatology, With Roy Fleischmann, MD

Chimeric Antigen Receptor (CAR) T-cell therapy cell therapy has demonstrated that drug-free remission in systemic lupus erythematosus (SLE) is achievable — but cost, infrastructure requirements, and the bluntness of current B-cell depletion approaches mean that T-cell engagers and next-generation monoclonal antibodies are likely to define the more immediately practical frontier of immunology-based therapy in rheumatology over the next decade.

To discuss where the field is headed, RheumatologyLive spoke with Roy Fleischmann, MD, Clinical Professor of Medicine at the University of Texas Southwestern Medical Center, Co-Medical Director of the Metroplex Clinical Research Center, and Co-Director of the Division of Rheumatology at Texas Health Presbyterian Hospital, Dallas, following his session on new molecules and modalities at the 2026 Rheumatology Winter Clinical Symposium, held in Maui, Hawaii, on February 11–14. Fleischmann — who has been involved in the development of virtually every medication approved for rheumatoid arthritis, psoriatic arthritis, and SLE in the United States — offered a measured but genuinely optimistic assessment of where cell-based and next-generation targeted therapies are heading, while cautioning that the earliest data across these modalities still involve very small patient numbers.

On CAR-T, Fleischmann acknowledged the striking early signal: the majority of patients treated in lupus trials achieved drug-free remission, establishing proof of concept that sufficiently deep immunologic reset can produce sustained disease control. The practical barriers, however, are substantial — cost, the need for specialized hospital infrastructure capable of delivering the therapy, the uncertain durability of remission, and the current reliance on lymphodepletion conditioning before infusion. His view is that CAR-T as currently constituted represents a first-generation proof of principle, and that meaningful clinical deployment will likely require another generation or 2 of refinement toward greater cellular specificity. T-cell engagers (TCEs) — bispecific antibodies that redirect T cells to deplete specific immune cell populations — are attracting more near-term enthusiasm among rheumatologists, Fleischmann noted, largely because they can be administered subcutaneously without the cell manufacturing and lymphodepletion requirements of CAR-T.

The key open questions for TCEs are durability and the degree to which they reproduce CAR-T's side effect profile: current first-generation TCE responses appear to last in the range of 3-9 months, leaving unresolved whether they are best deployed as induction therapy followed by a maintenance monoclonal antibody, or as a recurring intervention. Beyond cellular approaches, Fleischmann pointed to emerging monoclonal antibodies with more precise mechanisms — including plasma cell–targeting agents and improved B-cell depleters — as potentially obviating the need for TCEs entirely if used early enough in the disease course. The honest answer across all of these modalities, he emphasized, is that the patient numbers remain far too small to draw firm conclusions — but the directionality is clear, and the field is moving.

“There are some safety issues, but we also know, it's really, really expensive, and… the present therapies kill all the B-cells, and that's not really what you want to do. But CAR-T does tell you that if you have a very effective drug, you can actually get a patient into full remission,” Fleischmann said.

Flesichmann’s disclosures include AbbVie, Amgen, AstraZeneca, Bayer, Biogen, BMS, Boehringer Ingelheim, Eli Lilly, Flexion, Galapagos, Galvani, Gilead Sciences, GSK, Novartis, Pfizer, Regeneron, Roche, Samumed, Sanofi Aventis, UCB, Viela, and Vorso.

Reference

Fleischmann R. Rheumatology 2025: Year in Review. New and future therapies in Rheumatology. Presented at: RWCS 2026, held February 11-14 in Maui, Hawaii.