Three deaths in Novartis CAR T-cell therapy trials for autoimmune disease prompt caution

Novartis halts eight clinical trials of its CAR T-cell therapy, rapcabtagene autoleucel, on August 24, 2026, following three patient deaths from a rare immune reaction called HLH. While early trials show high efficacy for autoimmune diseases like lupus, these fatalities prompt caution. Experts note the deaths will require updated informed consent discussions, though they do not expect the safety setback to derail the promising therapy's overall development.

Novartis halts trials and investigates deaths

• ▪Novartis halted eight clinical trials of its cellular therapy rapcabtagene autoleucel on August 24, 2026, following the deaths of three patients from immune effector cell hemophagocytic lymphohistiocytosis.
• ▪The halted Novartis clinical trials of rapcabtagene autoleucel evaluated patients with lupus, rheumatoid arthritis, vasculitis, multiple sclerosis, and myasthenia gravis.
• ▪Novartis is conducting a comprehensive review of the three trial deaths and working with independent safety boards to analyze the causes and associated factors.

Treating hemophagocytic lymphohistiocytosis

• ▪Immune effector cell hemophagocytic lymphohistiocytosis is a rare, catastrophic immune reaction that can occur due to autoimmune disease or malignancy and must be treated aggressively with high-dose steroids.
• ▪Philip J. Mease, MD, stated that immune effector cell hemophagocytic lymphohistiocytosis can be treated with anakinra or certain chemotherapy agents.

Impact of deaths on patient participation

• ▪Philip J. Mease, MD, noted that the reported deaths in the Novartis trials may lead some patients with less refractory autoimmune diseases to decline entering clinical trials.
• ▪Philip J. Mease, MD, stated that the three participant deaths in the Novartis trials will require the inclusion of these events in future informed consent conversations with autoimmune patients.

Efficacy and risks in autoimmune conditions

• ▪Chimeric antigen receptor T-cell therapy in patients with systemic lupus erythematosus carries risks of cytokine release syndrome, neurotoxicity, infection, and long-term B-cell depletion.
• ▪A 2025 review article by Nordmann-Gomez and colleagues found that 70% of systemic lupus erythematosus patients achieved remission after receiving chimeric antigen receptor T-cell therapy.
• ▪Prior to the August 2026 trial deaths, the overall severity of side effects from chimeric antigen receptor T-cell therapy in autoimmune conditions was generally lower than in lymphoma patients.

Expanding Therapy Access to community sites

• ▪Dr. Porter stated that community-based chimeric antigen receptor T-cell therapy delivers clinical results comparable to academic care, supporting the expansion of these therapies to community sites.
• ▪Dr. Porter cited data that only 18% to 20% of eligible patients receive chimeric antigen receptor T-cell therapy, arguing community expansion is the only durable solution to close this access gap.
• ▪The Foundation for the Accreditation of Cellular Therapy has redesigned its standards specifically to make accreditation more accessible to community sites offering chimeric antigen receptor T-cell therapy.

Development of CAR T-Cell therapy

• ▪Renier Brentjens was one of four scientists awarded by the Warren Alpert Foundation in 2024 for his pivotal role in developing chimeric antigen receptor T-cell therapy.
• ▪Chimeric antigen receptor T-cell therapy, first approved in the United States in 2017, has demonstrated success in treating blood cancers, specifically B-cell cancers and multiple myelomas.

Improving cancer survival rates

• ▪Preventive screening programs and a decline in major risk factors like smoking contributed to the record-high cancer survival rate in the United States.
• ▪The American Cancer Society reported in January 2026 that the five-year survival rate of cancer in the United States reached 70%, the highest mark to date.

Debatable claims

• ▪Expanding CAR T-cell therapy to community sites compromises patient safety
• ▪CAR T-cell therapy is too dangerous to use for non-terminal autoimmune diseases