Novartis and BMS pause autoimmune CAR-T trials after serious immune-related events

Novartis has paused eight clinical trials of its experimental CD19 CAR-T therapy rap-cel (YTB323) for autoimmune and neurological diseases after three patients died from complications associated with a severe immune reaction called immune effector cell-associated hemophagocytic syndrome (IEC-HS).

The pause, implemented in late August, affects studies involving lupus, lupus nephritis, systemic sclerosis, vasculitis, inflammatory myopathies, rheumatoid arthritis, Sjögren’s disease, myasthenia gravis, and multiple sclerosis.

Novartis said it is conducting a comprehensive safety review with independent study-monitoring boards and regulators. Patients already treated will continue to be monitored.

The company described IEC-HS as a known, potentially life-threatening risk of CAR-T therapy. Its oncology CAR-T studies in leukemia and lymphoma are reportedly unaffected.

Bristol Myers Squibb has separately implemented a voluntary pause in enrollment in autoimmune trials of its rival CD19 CAR-T therapy zola-cel (BMS-986353), citing transient and reversible inflammatory events and a precautionary review of clinical data.

The developments raise concerns about whether the intense immune activation associated with CAR-T—which has shown promise in eliminating disease-causing B cells—can be managed safely in autoimmune patients, who may not face immediately life-threatening illness.