Landmark-Based Evaluations of Long-Term Outcomes After CD19 CAR T-Cell Therapy in Large B-Cell Lymphoma

CAR T-cell therapy has transformed relapsed/refractory large B-cell lymphoma (LBCL) treatment, yet durable remissions remain challenging. In this retrospective multicenter study, 479 LBCL patients treated with commercial CD19 CAR-T products, axicabtagene ciloleucel (axi-cel, n = 262), tisagenlecleucel (tisa-cel, n = 131), and lisocabtagene maraleucel (liso-cel, n = 86), were evaluated using serial landmark analyses, with median follow-ups of 23, 34, and 16 months, respectively. Progression-free survival (PFS) was assessed at Day 28 and at 3, 6, 12, 18 and 24 months post-infusion to determine when relapse risk declines and sustained disease-free remission is achieved. Patients who attained a complete response (CR) at early time points had significantly improved PFS. In multivariable analyses, elevated pre-lymphodepletion lactate dehydrogenase (LDH) levels were independently associated with inferior PFS across several landmarks (HR 2.67, P < .001 at Day 28; HR 1.83, P = .044 at 3 months; HR 2.19, P = .016 at 6 months) and showed consistent association with inferior overall survival (OS) at these same time points. Cumulative relapse and non-relapse mortality (NRM) estimates supported the prognostic value of sustained CR. This landmark-based analysis advances understanding of durable remission kinetics following CAR T-cell therapy, indicating a trend toward cure, though longer follow-up is needed to confirm durable remission.