Post by Mahnoush Bahjat

Hepatic effects of CAR‑T therapy: practical guidance for distinguishing expected toxicities from drug‑induced liver injury (DILI) as programs expand beyond oncology Proud to share this collaborative effort with the IQ DILI Initiative and the Immunotherapy Working Group, bringing together experts from pharma and academia to advance liver safety in immunotherapies: Anna Fettiplace (Quell Therapeutics), Arie Regev M.D., FAASLD (Eli Lilly and Company), Alexandre Kiazand (Immunocore), Ulrike Heinzel-Pleines (Bayer), Anju Garg (Sanofi), Luciana Kikuchi (USP - Universidade de São Paulo), Hewei Li (Johnson & Johnson Limited, Janssen-Cilag Pharmaceuticals), Ali Hamidi, MD (Amgen), David H. Alpers (Washington University), Hanns-Christian Tillmann (Novartis), DOMINIQUE LARREY (University of Montpellier), Adrian Di Bisceglie (KAD Clinical Research-St.Louis, MO), and James H. Lewis (Georgetown University Medical Center). CAR‑T therapies are moving rapidly from hematologic malignancies into solid tumors and non‑oncology indications. As programs expand, understanding the liver safety profile becomes critical for benefit–risk assessment. Our consortium review and expert consensus summarize: ▪️ Expected hepatic effects linked to cytokine release syndrome (CRS) and IEC‑HLH, including timing, magnitude, and patterns (e.g., AST > ALT in severe CRS; more frequent bilirubin rises in IEC‑HLH). ▪️ Under‑reporting challenges in trials and recommendations to improve MedDRA term precision and collection of bilirubin and INR alongside ALT/AST. ▪️ A structured work‑up to differentiate anticipated effects from alternative causes (infection, HBV reactivation, cardiac hypoperfusion, concomitant meds) and true DILI. ▪️ Practical first‑ and second‑line investigations to support causality assessment and decision‑making in trials. ▪️ Implications for non‑oncology CAR‑T development: lower cell doses, reduced tumor microenvironment inflammation, and rigorous baseline liver status can improve characterization of hepatic signals. For teams designing CAR‑T trials, this paper offers a usable framework to standardize liver safety evaluation and enhance data quality as indications broaden. This work aligns with the ongoing efforts at AstraZeneca and our Clinical Pharmacology & Safety Sciences (CPSS) organization to advance the right safety for patients with a special thanks to my colleagues, Dominic Williams for enabling my participation to this initiative and Julia Johansson, Richard Stebbings, Jorrit Hornberg for their support. Link to the paper: https://lnkd.in/eFcPNDfg #CART #Immunotherapy #LiverSafety #DILI #CRS #HLH #Hepatology #ClinicalTrials #Oncology #AutoimmuneDisease #Pharmacovigilance #PatientSafety #TranslationalScience #DrugDevelopment #pharmaceuticals #whatsciencecando