News of patient deaths and severe inflammatory reactions in Novartis and Bristol Myers Squibb’s autoimmune CAR T trials hit the rheumatology community hard. The shock was immediate. Spherix Global Insights’ latest report shows these safety events did more than shake confidence. They forced U.S. rheumatologists to rethink the entire immune reset field.
After the trial pauses, Spherix recontacted 76 U.S. rheumatologists. Their confidence in autologous CAR T therapies dropped sharply—from an average of 7.5 to 5.2 out of 10. The risk of serious side effects shot up as the main reason doctors hesitate to refer patients to trials. The focus has shifted. It’s no longer about spreading awareness. Now, it’s about rebuilding trust. Still, autologous CAR T kept its lead. Nearly half of surveyed rheumatologists ranked it as their first choice. It stayed ahead of T-cell engagers and in vivo CAR T options.
A systematic review of 38 studies involving 115 autoimmune patients found that cytokine release syndrome occurred in over 70% of cases, but most episodes were low grade.
Safety fears spread to all immune reset options
The fallout didn’t stop with autologous CAR T. Spherix’s data show that caution spread to every immune reset approach—autologous, allogeneic CAR T, CAR-NK, in vivo CAR T, and T-cell engagers. No platform gained ground from the setbacks. Instead, the whole field faces tougher scrutiny. Rheumatologists now want stronger safety evidence before they’ll consider any immune reset therapy for their patients.
On September 1, 2026, The Wall Street Journal reported that Novartis halted eight clinical trials of its experimental autoimmune and neurological CAR-T therapy, rap-cel, after three patient deaths tied to a rare, severe immune reaction called IEC-HS. Novartis kept its oncology-focused rap-cel studies running. The paused trials targeted autoimmune diseases like lupus, rheumatoid arthritis, multiple sclerosis, and systemic sclerosis, as detailed in an industry summary of Reuters reporting.
Bristol Myers Squibb also paused enrollment in its zola-cel program. The reason: "transient and reversible" inflammatory events. Unlike Novartis, no deaths were reported in the BMS trials. The pause was a precaution, not a full stop, according to Reuters coverage. These events have pushed doctors to demand more product-specific safety data. They want to know if risks are tied to a single therapy or if they’re a problem across the whole platform.
Industry analyses highlight that the FDA has not yet published dedicated guidance for CAR-T or T-cell engager therapies in autoimmune diseases. Sponsors are advised to seek early consultation with the Office of Therapeutic Products before submitting IND applications.
Even with all the turbulence, autologous CAR T still leads. Its evidence base is stronger. The promise of a one-time, personalized immune reset keeps it ahead. T-cell engagers and in vivo CAR T options attract interest for their off-the-shelf convenience and simpler logistics. They don’t require cell collection or outside manufacturing. But there’s a catch. Doctors still worry about how long these therapies last and their long-term safety. That keeps them from overtaking autologous CAR T.
Systemic sclerosis: the main target
Systemic sclerosis (SSc) stands out. Over two-thirds of rheumatologists say SSc is the top priority for immune reset therapies. It’s far ahead of idiopathic inflammatory myopathies and lupus nephritis. The consensus is clear. Immune reset will likely be used for patients with disease that resists other treatments, those with major organ involvement, or those who relapse after B-cell depletion. Early use will focus on the most severe cases. The risks and complexity may be worth it for these patients.
But there’s a big gap. The number of patients doctors think are eligible for immune reset is much higher than those they expect will actually get it. Access to specialized centers, safety worries, and travel burdens block the way. Spherix’s findings suggest that making these therapies available in outpatient settings and offering flexible care could help. Still, manufacturers will need to build networks that connect rheumatologists, specialty centers, and patients. Without that, the commercial promise won’t be realized.
Patient demand and tougher adoption standards
Patients with severe or hard-to-treat disease still want cell therapy. Before the recent safety scares, more than half of rheumatologists saw growing patient interest. But the same issues—safety, access, travel, and treatment intensity—now threaten to limit real-world use. The bar for adoption is higher. Only therapies that can prove they balance effectiveness, safety, and practicality will succeed.
For drug and biotech companies, the message is blunt. Efficacy alone is not enough. The market now wants clear, product-specific safety data. Companies must show whether risks are tied to a single product, a platform, or the whole class. As Spherix’s Sawyer May put it, companies need to know not just which therapy doctors prefer, but which patients will actually be chosen, what evidence will change behavior, and which care models can turn clinical interest into real-world use.
This reset mirrors what’s happened in other CAR T fields, like the reported earlier push to expand CAR T in oncology. Now, autoimmune diseases face their own reckoning. The commercial opportunity is still big. But the path to adoption is tougher than ever. Only companies willing to invest in both clinical evidence and delivery systems will have a real shot at turning physician and patient interest into actual uptake.
