[Beyond comorbidities: CAR-T as a safe and effective option in frail patients with second-line DLBCL.]

CD19 CAR-T therapy is the second-line standard for relapsed/refractory DLBCL, yet the management of frail patients remains debated due to toxicity and non-relapse mortality risks. We report a 74-year-old man with high-risk DLBCL and multiple comorbidities, refractory to first-line treatment, who received axicabtagene ciloleucel. Despite high CIRS and HCT-CI scores, he only developed grade 1 CRS successfully managed with early tocilizumab and transient cytopenia, achieving durable complete remission at 14 months. This case supports evidence from ALYCANTE and real-world cohorts showing comorbidities alone do not predict severe toxicities. Instead, dynamic parameters such as ECOG, mEASIX and CAR-HEMATOTOX better identify patients at risk. A priori exclusion of frail individuals may unjustly deny access to a potentially curative therapy.