Abstract
Most patients with large B-cell lymphoma (LBCL) progressing after CAR-T therapy experience poor survival and lack standardized treatment strategies. Prognostic tools are needed to guide decision-making at relapse. The Post-CAR Prognostic Index (PC-PI), recently proposed by Iacoboni et al., combines five routine clinical variables to stratify outcomes after CAR-T failure: ECOG (> 0), hemoglobin (< 10 g/dL), LDH (≥ 2xULN), number of extranodal sites (> 1) and time from CAR-T to progression (< 4 months). We evaluated the PC-PI in a retrospective multicenter study including 125 LBCL patients relapsing or refractory after axicabtagene-ciloleucel or tisagenlecleucel, treated between 2019 and 2023 across 16 Italian centers belonging to the Fondazione Italiana Linfomi network. Median overall survival (OS) was 4.9 months, with 6- and 12-month OS rates of 44.9% and 28.5%, respectively. The PC-PI discriminated prognosis effectively: high-risk patients had a median OS of 1.8 months, intermediate-high 2.2, intermediate-low 8.7, while in the low-risk group median OS was not reached (p<0.0001). Results remained consistent after excluding patients receiving only palliative care. Post-progression therapy markedly influenced survival: patients receiving active treatment achieved a median OS of 7.3 months versus 0.7 without further therapy (p<0.0001). Bispecific antibodies conferred the best outcomes (HR 0.44, p=0.02), with 6- and 12-month OS rates of 90% and 55%. Our findings confirm the prognostic value of the PC-PI and support its use in clinical practice as a tool for risk-adapted management of LBCL after CAR-T failure.