The emergence of B-cell– and T-cell–targeted strategies may help to expand treatment options for systemic lupus erythematosus (SLE). Established and emerging approaches such as belimumab, obinutuzumab, anifrolumab, dapirolizumab pegol, CAR T-cell therapy, and T-cell receptor (TCR) therapy were discussed at the Congress of Clinical Rheumatology (CCR) – East 2026.

Following these presentations, featured expert Kenneth Kalunian, MD, was interviewed by Conference Reporter Associate Editor-in-Chief Christopher Ontiveros, PhD. Clinical perspectives from Dr Kalunian on these findings are presented here.

B cells contribute to the pathogenesis of SLE well beyond autoantibody secretion. B cells in lupus are also antigen-presenting cells for T-cell activation and sources of proinflammatory cytokines. If you decrease the presence of B cells, you are going to have different effects that are positive in terms of mitigating SLE disease activity.

The B-cell therapy that we have been using for the longest time is belimumab. It was the first drug to be approved by the US Food and Drug Administration (FDA) specifically for SLE in the modern era. Belimumab inhibits BAFF, a survival factor for autoantibody-producing B cells, and is very helpful for joint manifestations and, to a lesser extent, skin disease. We think that the driver of joint manifestations in SLE is more related to B-cell dysregulation than innate immune system dysregulation, while skin manifestations may be more related to innate immune system dysregulation. Belimumab is often used as part of the “triple therapy approach” for lupus nephritis, given its effects on a disease manifestation that is highly related to B-cell hyperactivity. One limitation with belimumab, however, is that it takes a while to work in skin and joint manifestations.

Obinutuzumab is another important B-cell–directed therapy. The REGENCY study of obinutuzumab, which was discussed by Alfred H. Kim, MD, PhD, during his presentation at CCR East 2026, demonstrated beneficial efficacy in lupus nephritis. Also presented at CCR East 2026 were the top-line results from the ALLEGORY trial by Richard A. Furie, MD, and colleagues for non-nephritis lupus. In ALLEGORY, patients who received obinutuzumab did much better on the primary end point (ie, the SLE Responder Index 4 [SRI-4] at week 52 vs placebo), demonstrating an improvement in flare reduction and remission rates. Grade 3 or higher adverse events were observed in 16.6% of patients in the obinutuzumab group and 13.9% of those in the placebo group, and serious adverse events were reported in 15.9% and 11.9%, respectively. The conclusion is that obinutuzumab was superior to placebo in the primary and the 5 key secondary end points, and no significant new safety issues were observed.

Obinutuzumab is now FDA approved for active lupus nephritis in adults undergoing standard treatment. In the future, it may assist in our ability to care for patients who do not respond to belimumab or anifrolumab for severe skin and joint activity. Obinutuzumab may also help patients who have more widespread disease beyond skin and joint manifestations, such as those with hemolytic anemia, thrombocytopenia, and central nervous system disease.

Dapirolizumab pegol, an anti-CD40 ligand therapy, is an interesting molecule in SLE because it targets the interaction between B cells and T cells. An updated analysis by Eric F. Morand, MBBS, PhD, et al from the phase 3 PHOENYCS GO study evaluating low disease activity and remission achievement was presented at CCR East 2026, and there is a second ongoing phase 3 study to confirm the results.

T cells have not been studied as often in lupus clinical trial development because we have thought of SLE as more of a B-cell effect–driven disease. Where T cells are coming in now as potential SLE treatment targets is with CAR T-cell and TCR therapies. I think that TCR therapy may be more predominant than CAR T-cell therapy moving forward due to easier administration, and it may require less intensive conditioning. Simply speaking, with T-cell–targeted therapy, we are using T cells as an adjunct to kill B cells.

CAR T-cell therapy was also part of the CCR East 2026 discussion, with 2 phase 1 studies in SLE by Jennifer L. Medlin, MD, and colleagues and David Simon, MD, et al presented during the meeting. Although the risk of cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome did not appear to be a significant safety issue in what they presented, even a low degree of risk, for me, is concerning when we have these other drugs that are so effective and do not have these types of potential side effects. The argument for the potential use of CAR T-cell therapy is that it could be “one and done,” meaning that you provide durable treatment-free disease remission. However, we have incomplete long-term safety data at the present time.