September 1, 2026 /
As with all new technologies, when they are being transferred from oncology to autoimmunity, there may be some hurdles to overcome
GAVIN GIOVANNONI — SEP 1, 2026
You may have heard that three study subjects have died in Novartis’ CD19-directed CAR-T treatment trials as a result of immune effector cell-associated hemophagocytic syndrome. This condition occurs when the immune system becomes hyperactive, and complications lead to fatal outcomes.
Immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) is a rare, severe, and potentially life-threatening hyperinflammatory complication that can occur after treatments like CAR T-cell therapy or bispecific antibodies. It resembles secondary hemophagocytic lymphohistiocytosis (HLH), an aggressive condition driven by an overactive immune response. Key features include a massive surge of immune signals and cytokines and very high levels of ferritin in the blood (hyperferritinaemia). There is a rapid drop in red and white blood cells and platelets (pancytopaenia). It is associated with multiorgan dysfunction, primarily affecting the liver and blood clotting. It differs from cytokine release syndrome (CRS), which also causes inflammation after cellular therapy, but IEC-HS is recognised as a distinct entity that typically presents or persists independently after CRS has resolved.
Novartis’ treatment is known as rapcabtagene autoleucel, or rap-cel, and is being tested in systemic lupus erythematosus/lupus nephritis; systemic sclerosis; antineutrophil cytoplasmic antibody-associated vasculitis; idiopathic inflammatory myopathies; rheumatoid arthritis and Sjogren’s disease; generalised myasthenia gravis; and relapsing multiple sclerosis and non-active progressive MS.
Bristol Myers Squibb (BMS) has also paused enrollment in its autoimmune trials for zolacabtagene autoleucel, or zola-cel, another CD19 CAR-T, due to transient and reversible inflammatory events during routine study surveillance. The overall safety profile of BMS’ product remains consistent with the known profile of CAR-T therapies.
This comes on the back of the three deaths of patients receiving an experimental genetic medicine from a biotech startup in China, RiboX Therapeutics. RiboX’s treatment, called RXIM002, belongs to a class of experimental medicines known as in vivo CAR-T therapy. The treatment reprograms a patient’s T cells, in vivo, to destroy misbehaving B cells, which cause many autoimmune diseases and blood cancers. The latest death was a man with severe systemic sclerosis and significant pre-existing medical issues.
Many of these new products involve so-called rapid CAR T-cell manufacturing platforms or, in the case of the Chinese product, in vivo engineering. Whether or not the toxicities could be linked to these new manufacturing processes is unknown. Hopefully more information will become available to determine the causes of death and the mechanisms behind them. These setbacks are worrying for the field. Let’s hope the CAR T-cell community can find the cause and address the mechanisms to make these therapies safer for people with MS.
Sources
I have received emails from several concerned individuals. My advice is to stay calm and wait for all the details to emerge. As with all new technologies, when they are being transferred from oncology to autoimmunity, there may be some hurdles to overcome. We have extensive experience repurposing oncology products for MS, including HSCT, alemtuzumab, cladribine, and anti-CD20. I am optimistic that engineered T-cells will also become an option to treat MS and other treatment-resistant autoimmune diseases in the future. We are only at stage 1 of the development pathway for CAR T-cells in MS. We need to persevere and move forward slowly.
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