Late failure outcomes post CAR T-cell therapy in LBCL: A real-world study

A retrospective cohort study from the DESCAR-T registry analyzed features, treatments, and outcomes of 298 patients with large B-cell lymphoma (LBCL) who experienced late failure, defined as progression or relapse occurring >3 months after chimeric antigen receptor (CAR) T-cell therapy. Most patients had diffuse large B-cell lymphoma (DLBCL; 68.8%), advanced stage disease (84.6%), and an age-adjusted International Prognostic Index (aaIPI) of 2–3 (59.3%) at CAR T-cell eligibility. The primary endpoints assessed were progression-free survival 2 (PFS-2) and overall survival 2 (OS-2). Findings were published by Erbella et al. in Blood Advances.

Key data: After late failure, 76.5% of patients received a systemic therapy, with an overall response rate (ORR) of 22.6% and a complete response rate (CRR) of 18%. At a median follow-up of 13.8 months since the first late failure event, the median PFS-2 and OS-2 were 4.4 months (95% confidence interval [CI], 3.8–5.8 months) and 13.2 months (95% CI, 9.6–18 months), respectively. Bispecific antibodies (BsAbs) demonstrated superior PFS-2 compared with chemotherapy (hazard ratio [HR], 0.350; 95% CI, 0.193–0.633; p = 0.0005) and pooled other treatment groups (HR, 0.483; 95% CI, 0.290–0.805). Radiotherapy achieved durable responses with a 12-month PFS-2 rate of 41.5% in evaluable patients..

Key learning: The findings show that outcomes remain poor in patients with LBCL and late failure after CAR T-cell therapy. BsAbs represent the most effective salvage strategy in this population, achieving superior PFS-2 compared with other treatments.