The impact of IPI risk factors on CAR T-cell therapy or allogeneic stem cell transplantation for treatment of relapsed or refractory large B-cell lymphoma (LBCL)

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Abstract
The International Prognostic Index (IPI) is an essential prognostic tool for patients with large B-cell lymphoma (LBCL). To compare outcomes after chimeric antigen receptor T-cell (CART) therapy and allogeneic stem cell transplantation (alloSCT) in relation to IPI risk factors, we analyzed 515 LBCL patients receiving CART (n = 303) or alloSCT (n = 212) as ≥third-line treatment, registered with EBMT (2016–2021). Patients treated with CART were older (median 62.4 vs 51.1 years), had higher IPI scores (48.2% vs 20.8% high/high-intermediate risk), and a higher incidence of refractory disease (84.1% vs 34.6%). At 24 months, overall survival (OS) was 49% vs 41%, progression-free survival (PFS) was 37% vs 32%, relapse-incidence (RI) was 56% vs 38%, and non-relapse-mortality (NRM) was 7% vs 30%, respectively. In multivariate analysis, CART therapy showed superior OS primarily due to significantly lower NRM, while RI was higher. The survival benefit of CART was significant in patients with low/low-intermediate IPI (OS HR 0.43, 95% CI 0.31-0.60), but not observed in high-risk patients. Elevated LDH eliminated the PFS advantage of CART over alloSCT. Poor outcomes after CART in patients with high-risk disease support early preparation for alloSCT for eligible patients.

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