SNUH-CD19-CAR-T(Seoul National University Hospital)

Elderly LBCL patients have unfavorable clinical and biological features, leading to higher relapse rates. While CD19 CAR-T therapy offers a curative option in second-line, access remains limited by clinical criteria in pts aged ≥ 65 years. In our real-world study, we evaluated 232 LBCL pts ≥ 65 years focusing on first line outcomes and potential CAR-T eligibility. Sixty-four patients progressed or relapsed. Applying AIFA criteria, only 9/37 (24%) R/R LBCL pts aged 65-75 years would have been CAR-T eligible. Among those > 75 years, excluded from CAR-T in Italy, only 3/27 (11%) met eligibility criteria. The main exclusion criteria were ECOG ≥ 2 (34 pts, 53%), CNS involvement (14 pts, 22%) and rapidly progressive disease with life expectancy < 12 weeks (12 pts, 19%) The majority of pts who would have been excluded from CAR-T therapy had multiple criteria (32/52, 61%). Pts not receiving full-dose anthracyclines would have been seldom candidates for CAR-T (only 2/12, 16.5%). This study provides an estimate of the potential eligibility to CAR-T cell therapy in an elderly population of R/R LBCL in a real world setting of a CAR-T center. These findings highlight the urgent need for improved first-line therapies for elderly R/R LBCL pts.

Recent reports have raised concerns about the association of chimeric antigen receptor T cell (CAR‐T) with non‐negligible cardiotoxicity, particularly atrial arrhythmias. First, we conducted a pharmacovigilance study to assess the reporting of atrial arrhythmias following CD19‐directed CAR‐T. Subsequently, to determine the incidence, risk factors and outcomes of atrial arrhythmias post‐CAR‐T, we compiled a retrospective single‐centre cohort of non‐Hodgkin lymphoma patients. Only commercial CAR‐T products were considered. Atrial arrhythmias were nearly fourfold more likely to be reported after CAR‐T therapy compared to all other cancer patients in the FAERS (adjusted ROR = 3.76 [95% CI 2.67–5.29]). Of the 236 patients in our institutional cohort, 23 (10%) developed atrial arrhythmias post‐CAR‐T, including 12 de novo arrhythmias, with most (83%) requiring medical intervention. Atrial arrhythmias frequently co‐occurred with cytokine release syndrome and were associated with higher post‐CAR‐T infusion peak levels of IL‐10, TNF‐alpha and LDH, and lower trough levels of fibrinogen. In a multivariable analysis, risk factors for atrial arrhythmia were history of atrial arrhythmia (OR = 6.80 [2.39–19.6]) and using CAR‐T product with a CD28‐costimulatory domain (OR = 5.17 [1.72–18.6]). Atrial arrhythmias following CD19‐CAR‐T therapy are prevalent and associated with elevated inflammatory biomarkers, a history of atrial arrhythmia and the use of a CAR‐T product with a CD28 costimulatory domain.