Impacts of CAR T-cell therapy in lupus often ‘not captured on SLEDAI’
Chimeric antigen receptor T-cell therapy improves not only lupus disease activity but also other related conditions that impact quality of life, according to a speaker at the Basic and Clinical Immunology for the Busy Clinician symposium.
According to Emily Littlejohn, DO, MPH, of the department of rheumatologic and immunologic disease at the Cleveland Clinic, which hosted the symposium, these include fatigue and Jaccoud’s arthropathy. In her talk, she described outcomes for three patients who underwent CAR T-cell therapy to help attendees understand what can be expected in terms of efficacy and outcomes.
“Three patients all enrolled on renal criteria with very different but very significant other manifestations of lupus, but also with some social stressors and barriers,” she said.
The first patient was a woman aged 30 years with lupus nephritis class V, lupus hepatitis, lymphadenopathy, inflammatory arthritis, discoid lupus erythematosus and alopecia. The second was a woman aged 27 years with lupus nephritis class IV and V, hemolytic anemia, Jaccouds arthropathy, acute cutaneous lupus and pleural/pericardial effusions. The third was a man aged 20 years with lupus nephritis class IV and V, pericarditis with large pericardial effusions, acute cutaneous lupus and alopecia.
Results for the first patient showed resolution of discoid lesions, alopecia, mucocutaneous ulcers and lymphadenopathy at day 29 following CAR T-cell therapy.
“Also, her proteinuria resolved at day 57, which was pretty incredible,” Littlejohn said.
Meanwhile, the patient’s Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) fell from 7 to 0 by day 29, she added.
However, Littlejohn stressed that disease activity is only part of the overall response that matters to patients.
“What is most important here are the things that were not able to be captured in her SLEDAI,” Littlejohn said. “She became so much more active and was sleeping so much less. She wanted to go off disability and work.”
Researchers observed a similar phenomenon for the second patient, whose face rash, alopecia and proteinuria improved by day 29 after CAR T-cell therapy.
“Her proteinuria improved by a fourth at day 29, which was pretty incredible,” Littlejohn said.
In addition, her SLEDAI decreased from 12 at screening to 4 at day 141.
For this patient, Jaccoud’s arthropathy had been a significant barrier to improving quality of life, according to Littlejohn.
“She was not able to have a significant range of motion of her hands,” she said. “Around day 70, she had less clicking and much more range of motion in her joints.”
In the third patient, all cutaneous manifestations, including facial rash and discoid lesions, improved after CAR T-cell therapy, along with a reduction in proteinuria from 7 g to 2.4 g at day 70 after the procedure, according to Littlejohn. His joint swelling additionally improved and he demonstrated a reduction in SLEDAI from 18 at screening to 4 at day 57.
“Again, things that are not captured on SLEDAI that are really affecting his quality of life are that his fatigue is improving and he was stronger and had more stamina with exercise,” Littlejohn said. “He was able to get to his final exams.”
One of the most important take-home messages from these results pertains to the concept of remission for patients like these, according to Littlejohn. “Every day that goes by, we feel more comfortable using the word ‘remission’ in lupus,” she said.
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Littlejohn E. Clinical Outcomes of CAR-T cell therapy. Presented at Basic and Clinical Immunology for the Busy Clinician, Feb. 27, 2025; virtual meeting.