Post CAR-T Measurable Residual Disease Monitoring in Mantle Cell Lymphoma Enables Early Detection of Disease Relapse

CD19-directed chimeric antigen receptor (CAR) T-cell therapy has transformed outcomes for patients with relapsed or refractory (r/r) mantle cell lymphoma (MCL), yet more than 40% relapse within one year. Early identification of patients at risk for progression could inform post CAR-T surveillance and consolidation strategies. Measurable residual disease (MRD) has emerged as a powerful prognostic biomarker in frontline MCL, but its role after CAR T-cell therapy remains incompletely defined. We retrospectively analyzed 37 patients with r/r MCL treated with brexucabtagene autoleucel (brexu-cel). MRD was assessed using next-generation immunoglobulin high-throughput sequencing (Ig-HTS) of peripheral blood mononuclear cells obtained before lymphodepletion, at 1- and 3-months post-infusion, and every 3 months thereafter. Clonotype identification was successful in 36 of 37 patients. Pre-lymphodepletion MRD levels were lower in patients receiving bridging therapy (337 [0-198 449] vs. 21 213 [1-788 251]; p = 0.04), and MRD undetectability trended toward improved progression-free survival (PFS; unreached vs. 28.5 months; HR 5.2; p = 0.07). Post-infusion, patients with detectable Day 28 MRD had inferior PFS compared with those with undetectable MRD (10.9 vs. 51.5 months; HR 3.99; p = 0.002), whereas Day 28 PET-CT response did not correlate with PFS (p = 0.35; HR 1.8). Longitudinal MRD monitoring identified relapse a median of 6.5 months before PET/CT in most relapsing patients (15 out of 18). Early and serial MRD monitoring is thus a sensitive prognostic and surveillance tool in brexu-cel treated MCL, with Day 28 MRD serving as an early predictor of long-term outcomes.