• Informed consent talks regarding CAR T-cell therapy in autoimmune disease will have to include the newly reported trial deaths.
• Patients with less refractory disease may decline to enter trials.

HUNTINGTON BEACH, Calif. — The deaths of three participants in trials of Novartis’ chimeric antigen receptor T-cell therapy for autoimmune disease will “add some sobriety” to discussions with patients, according to a speaker.

“We’re in the very early days of learning about this,” Philip J. Mease, MD, MACR, FRCP, director of the rheumatology clinical research division at Swedish Medical Center/Providence St. Joseph Health, in Seattle, told Healio in an interview. “But it will have an impact on the ongoing efforts to get these therapies tested and approved, because we’re going to need to include discussion about these events in our informed consent conversation with patients.”

Novartis on Aug. 24 halted eight trials of its cellular therapy rapcabtagene autoleucel, also called rap-cel, in patients with lupus, rheumatoid arthritis, vasculitis, MS and myasthenia gravis following the deaths of three patients from immune effector cell hemophagocytic lymphohistiocytosis (HLH), according to reports. The company told Reuters it is conducting a comprehensive review of the deaths and working with independent safety boards to review the causes and associated factors.

In a presentation on the use of cell therapy in autoimmune disease at the Congress of Clinical Rheumatology West, Mease updated attendees on what is currently known about the safety of CAR T-cell therapy in lupus and other rheumatic conditions. Specifically regarding patients with systemic lupus erythematosus, he cited risks for cytokine release syndrome, ICANS and infection.

“There can be issues, including the fact that there may be some patients who don’t fully respond,” he told attendees. “There may be patients who have relapse. And then there are the safety issues associated with this long-term period of B-cell depletion that we’re instituting and waiting for the B cells to come back.

“In general, in the autoimmune conditions, the overall severity of these side effects have been less than what we have seen in patients with lymphoma — until recently,” he added. “[The presence of HLH in CAR T-cell trials] is a very unfortunate new development, but one that we have to be ready to anticipate and jump on with aggressive therapy.”

According to Mease, HLH is a “fairly catastrophic” and rare immune reaction that is more often seen in adolescents with a genetic proclivity but can also occur due to autoimmune disease or malignancy. HLH must be treated “very aggressively” with high-dose steroids, as well as anakinra or certain chemotherapy agents, he added.

He said the complication is rarely fatal.

“Patients may be in the intensive care unit, but it’s very uncommon to have fatality from it,” he told Healio. “We don’t know all of the story yet about these Novartis patients. We don’t know how quickly the investigative teams jumped on the problem and treated the patients aggressively. We don’t know the inflammatory state of the patients at the time this complication developed. And we also don’t have any clue about whether or not it’s related to anything about the actual CAR T-cell product.”

In his presentation, Mease cited several studies demonstrating dramatic improvement of disease activity among patients with SLE, RA and systemic sclerosis who received cell therapy. A 2025 review article by Nordmann-Gomez and colleagues, which included 145 patients from 16 studies of CAR T-cell therapy in SLE, found 70% of patients overall achieved Definition of Remission in SLE (DORIS) remission, while 89% achieved low disease activity and 84% reported drug-free remission.

Meanwhile, a dual-target CD19/BCMA CAR T-cell therapy yielded “profound, sustained” remission in 11 patients with refractory SSc, according to data presented at the EULAR 2026 Congress.

“We’ve had a great deal of very positive data about the efficacy of these approaches, including some patients with lupus in particular that have had very long-term and durable remissions from their disease,” Mease told Healio.

“We’ve been entering quite a number of patients into these clinical trials with good success and we are actively recruiting and enrolling for a variety of trials,” he added.

Mease does not expect the recent news from Novartis will slow the pace of research into CAR T-cell therapy for autoimmune disease.

“I don’t think this is going to derail this therapeutic approach, because it’s just too promising to too many patients to throw the baby out with the bath water,” he said. “But I do think it will add some sobriety to our conversations about risk, and some patients who are not as refractory may elect not to go into trials.

“Nonetheless, I think we won’t want to stop science and the really striking and significant responses that our patients with primarily B-cell driven diseases — such as lupus, scleroderma, myositis, rheumatoid arthritis and Sjögren’s disease — are seeing from going forward with these promising new therapies.”

Philip J. Mease, MD, MACR, FRCP, can be reached at pmease@philipmease.com.