Will Patient Deaths Derail the CAR-T Train in Autoimmune Disease?

Two major pharmaceutical firms have temporarily halted their ongoing clinical trials of chimeric antigen receptor (CAR) T-cell therapies for autoimmune diseases after reports of severe adverse events, including three fatalities. Novartis suspended enrollment in its rapcabtagene autoleucel (rap-cel) trials following three fatal cases of immune effector cell-associated hemophagocytic syndrome (IEC-HS).

Bristol Myers Squibb (BMS) halted its zolacabtagene autoleucel (zola-cel) program due to unspecified transient and reversible inflammatory events. The suspensions were first reported by Fierce Biotech, with no immediate response from Novartis and BMS providing a statement confirming the report without detailing further information.

ClinicalTrials.gov lists nine rap-cel trials across various autoimmune and other conditions, while BMS has three zola-cel trials targeting SLE, systemic sclerosis, and autoimmune cytopenia. CAR T-cell therapy, initially developed for B-cell-driven cancers, has shown remarkable success in autoimmune diseases by targeting aberrant B-cell activity.

However, the treatment carries risks, including cytokine release syndrome and, rarely, immune effector cell-associated neurotoxicity syndrome (ICANS). IEC-HS, a severe complication known in hematologic cancer applications, has not been reported in autoimmune disease patients, even though it's a rare side effect. While BMS maintains that the overall safety profile of zola-cel remains consistent with other CAR T therapies, the fatal events pose a significant concern.

The companies' decisions to pause trials raise questions about the safety and feasibility of bringing CAR T-cell therapy to market for autoimmune diseases, especially given the low life expectancy associated with these conditions.