CAR-T safety events dent rheumatologist confidence, Spherix finds

Rheumatologist confidence in autologous CAR-T therapy dropped significantly following safety events reported by two major pharmaceutical companies in late August, according to market intelligence firm Spherix Global Insights. Its 2026 Special Topix report on cell therapy in rheumatology found that mean physician confidence fell from 7.5 to 5.2 on a ten-point scale after news broke that Novartis had paused autoimmune trials of rapcabtagene autoleucel following three patient deaths, and that Bristol Myers Squibb had paused trials of zola-cel following inflammatory adverse events.

The study initially surveyed 105 US rheumatologists between 29 July and 7 August 2026, before rapidly recontacting 76 of the same physicians between 1 and 3 September, providing a longitudinal before-and-after view of how the safety disclosures reshaped physician sentiment in near real time.

Autologous CAR-T holds its ground

Despite the decline in overall confidence, autologous CAR-T retained its relative lead among the modalities evaluated. In the post-event survey, 49% of rheumatologists ranked autologous CAR-T as their first choice, compared with 28% for T-cell engagers and 16% for in vivo CAR-T. Spherix attributed this to the modality's more established evidence base and its potential for a personalised, one-time immune reset, rather than to any restoration of confidence following the safety reports.

Importantly, the caution did not simply redirect toward competing platforms. Concerns about risk extended to allogeneic CAR-T, CAR-NK, in vivo approaches and T-cell engagers, suggesting that developers of next-generation immune reset technologies should not assume they will automatically inherit physician enthusiasm lost by conventional autologous CAR-T.

Sawyer May, Rheumatology Insights Director at Spherix, noted the shifting commercial dynamic. "The commercial opportunity remains significant, but the path to adoption is becoming more nuanced," he said. "Companies need to understand not only which modality physicians prefer, but which patients they will actually nominate, what evidence will change behaviour, and which care models can convert clinical interest into real-world use."

Systemic sclerosis leads on unmet need

Among the nine autoimmune conditions evaluated, systemic sclerosis stood out clearly as the area where rheumatologists perceive the greatest unmet need for immune reset therapy. More than two-thirds of physicians ranked it first, ahead of idiopathic inflammatory myopathies and lupus nephritis. Physicians most commonly viewed immune reset as appropriate for patients with refractory or treatment-resistant disease, significant organ involvement, or relapse following B-cell depletion.

The survey also highlighted a structural gap between the patients physicians consider clinically suitable for immune reset and those likely to receive it. Access to specialised cell and gene therapy centres, safety concerns and patient travel burden are among the barriers expected to narrow the treatable population. Nearly seven in ten rheumatologists said outpatient availability would make them more likely to prescribe or refer, and approximately two-thirds expressed openness to referral-based or hybrid shared-care models.

Broader competitive and regulatory context

The autoimmune CAR-T space has grown quickly over the past two years, driven partly by high-profile case series showing durable responses in refractory lupus and related conditions. Several companies beyond Novartis and Bristol Myers Squibb are advancing programmes in this area, including smaller biotechs developing allogeneic and in vivo platforms that aim to sidestep the manufacturing and logistics burden of conventional autologous approaches.

The recent trial pauses arrive at a pivotal moment. Regulators including the FDA and EMA are paying close attention to safety signals in haematological CAR-T that may have read-across implications for autoimmune indications, where patients are generally less ill than those enrolled in oncology trials and where the risk-benefit calculus is therefore stricter. Manufacturers will need to demonstrate, with product-specific data, whether observed adverse events are compound-related, platform-related or a class effect, a distinction that will shape both physician willingness to refer and regulator appetite for broader approvals.

For the field as a whole, the Spherix findings underline that the commercial challenge in autoimmune cell therapy is increasingly as much about delivery infrastructure and physician confidence as it is about clinical efficacy.