Allogene Therapeutics has reported a patient death attributable to ALLO-647, an anti-CD52 monoclonal antibody used for lymphodepletion in its pivotal CAR-T cell therapy (cema-cel) trial for large B-cell lymphoma (LBCL)1.
The death occurred in the Phase 2 ALPHA3 trial, which is key for the company’s allogeneic anti-CD19 CAR-T product used as first-line consolidation therapy in LBCL1.
The fatal event was liver failure, believed to be the consequence of disseminated adenovirus infection while the patient was immunosuppressed due to ALLO-647 administration (along with fludarabine and cyclophosphamide)1.
Allogene stated the death was not linked to the CAR-T product itself (cema-cel), but to ALLO-647, which is employed to enhance lymphodepletion and thus support CAR-T engraftment1.
Following the incident, Allogene has discontinued the use of ALLO-647 in this and potentially other relevant studies14.
Prior publications had found the ALLO-647-based lymphodepletion regimen generally tolerable, without prior substantial reports of grade ≥3 cytokine release syndrome, neurotoxicity, or graft-versus-host disease, and with infection rates comparable to autologous CAR-T therapy3.
Sources:
1. https://www.fiercebiotech.com/biotech/allogene-reports-patient-death-and-discontinues-investigational-antibody-phase-2-trial
3. https://allogene.com/wp-content/uploads/2025/04/locke-et-al-2025-allogeneic-chimeric-antigen-receptor-t-cell-products-cemacabtagene-ansegedleucel-allo-501-in-relapsed.pdf
4. https://www.cellgenetherapyreview.com/3972-News/620663-Allogene-changes-CAR-T-study-design-following-patient-death-from-lymphodepletion-regimen/