Rob Volansky , 2025-05-04 09:30:00
DESTIN, Fla. — An increasing array of B-cell targeting approaches may aid clinicians in managing the cycles and flares of lupus, according to a speaker at the Congress of Clinical Rheumatology East annual meeting.
“I like to think about lupus as an evolving cycle that repeats,” J. Michelle Kahlenberg, MD, PhD, professor of internal medicine and dermatology, Giles Boles and Dorothy Mulkey research professor of rheumatology, and vice chair of basic and translational research in the department of internal medicine at the University of Michigan, told attendees. “Every organ in the body is basically fair game to have lupus attack or evolve there.”
“We have to learn more about this disease to provide more personalized treatment for our patients,” Michelle Kahlenberg, MD, PhD, told attendees. Image: Rob Volansky | Healio
According to Kahlenberg, although B-cell activation is “important for many patients” with lupus, treatment needs to be tailored and individualized.
For example, belimumab (Benlysta, GlaxoSmithKline) can be used to “reset the balance” of the immune system, rather than depleting it entirely, she said.
“But this takes time,” Kahlenberg added, noting that the effect of belimumab is often seen only after 24 weeks of treatment in trials. “Belimumab may work better for short-lived B-cell problems.”
This is not the only attractive quality this medication has demonstrated.
“Belimumab lowers flare rates and steroid use,” Kahlenberg said.
Rituximab (Rituxan, Genentech) offers another strategy for B cells.
“Rituximab does not deplete most plasma cells,” Kahlenberg said. “Rituximab will fix short-term problems in the plasmablast population.”
For physicians looking for another approach, Kahlenberg suggested that obinutuzumab (Gazyva, Genentech) may have strong B-cell depleting properties despite being an anti-CD20 therapy.
Looking deeper into the armamentarium for specific patients, Kahlenberg suggested that the addition of voclosporin (Lupkynis, Aurinia Pharmaceuticals) and belimumab to standard of care in lupus nephritis may improve response rates.
“Obinutuzumab may also have benefits in lupus nephritis and a positive effect on systemic disease markers,” she added.
However, regardless of which option or regimen is used, Kahlenberg stressed the importance of managing expectations for all of these medications.
“None of these generate long-lasting remission,” she said.
Meanwhile, the biggest question in lupus treatment, at the moment, pertains to chimeric antigen receptor (CAR) T-cell therapy and bispecific T-cell engager (BiTE) therapy. For Kahlenberg, the issue comes back to the cyclical nature of the disease.
“Will the cycle eventually catch up to patients who have gone through CAR T-cell therapy? Does innate immune dysfunction disappear with CAR T or BiTE? Interferon responses and long-term remission will depend on these factors,” she said.
Despite these big questions, there is one certainty for all players involved in lupus management.
“We have to learn more about this disease to provide more personalized treatment for our patients,” Kahlenberg said.
Sources/Disclosures
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Kahlenberg JM. Mechanisms Driving Lupus, Its Flares, and Subsequent Complications: Can New Therapeutic Avenues be Preventative or Decrease Disease Severity? Presented at The Congress of Clinical Rheumatology East; May 1-4, 2025; Destin, Florida (hybrid meeting).
Disclosures:
Kahlenberg reports consulting fees from AstraZeneca, Bristol Myers Squibb, Biogen, Boehringer Ingelheim, DangerBio, Eli Lilly & Co., Exo Therapeutics, Gilead Sciences, GlaxoSmithKline, Lupus Therapeutics, Rome Therapeutics, Thirona and Ventus Therapeutics; as well as grants from Bristol Myers Squibb, Janssen, Rome Therapeutics and Ventus Therapeutics.
