COMPARATIVE ACCURACY OF ALTERNATIVE EARLY MEASURES OF RESIDUAL DISEASE AFTER CAR19 THERAPY OF RELAPSED/REFRACTORY LBCL

Introduction: Over half of relapsed/refractory large B-cell lymphoma (rrLBCL) patients receiving anti-CD19 chimeric antigen receptor (CAR19) T-cells experience subsequent relapse. Improved methods are therefore needed to predict outcomes, and accurately measure minimal residual disease (MRD). While PET/CT metabolic response ∼4 weeks after CAR infusion is established for such early assessments, several liquid biopsy MRD (including IgHTS CAPP-Seq) have been reported noninvasively responses (Frank et al. JCO, 2021; Sworder ICML-16). Phased variant enrichment detection sequencing (PhasED-seq) allows further improved sensitivity detect circulating tumor-derived DNA (ctDNA) by monitoring phased-variants (PVs), comprising multiple independent somatic mutations in individual cell-free fragments. Here, we compared ∼week-4 evaluations PET/CT, CAPP-Seq, PhasED-Seq standard care axicabtagene ciloleucel (axi-cel) CAR19 therapy (Sworder al., Cancer Cell, 2023). Methods: Tumor or baseline plasma matched PBMC samples were used genotype SNVs PVs, with evaluation status on-treatment CAPP-Seq (SNVs) (PVs). We empirically determined an analytical at least 1:1e5 result optimal performance CAR19. Patients considered evaluable analyses having week +4 adequate available allowing sensitivity. was assessed Deauville 5-point score per Lugano criteria. Results: A total 29 all 3 (PET/CT, PhasED-Seq). detectable this landmark had inferior event-free survival (EFS) [log-rank p = 0.00018, Cox HR 7.88 (95% CI: 1.9–33.3); Figure 1A]. positivity 0.0028, 3.02 1.4–6.6), 1B] failure achieve a complete (Deauville 1–3) 0.015, HR=2.78 1.1–6.6); 1C] also associated EFS, however, outperformed both these predicting clinical outcomes. When considering discordant ctDNA between +4, detected additional that ultimately relapsed (Figure 1D). Among failed demonstrated 100% specificity identifying which would not progression 1E). Keywords: cellular therapies, diagnostic prognostic biomarkers, Conflicts interests pertinent the abstract B. J. Consultant advisory role: Foresight Diagnostics S. K. Alig Honoraria: Takeda M. Shahrokh Esfahani H. Baird Research funding: Kite Pharma Y. Natkunam Leica Biosystems, Roche R. G. Majzner Lyell Immunopharma, NKarta, Arovella Pharmaceuticals, Innervate Radiopharmaceuticals, GammaDelta Therapeutics, Aptorum Group, Zai Labs, ImmunAI, Gadeta, FATE Therapeutics (DSMB), Waypoint Bio Stock ownership: Link Cell Therapies, CARGO C. L. Mackall Lyell, CARGO, Link, Apricity, Nektar, Immatics, Mammoth, Ensoma. Therapies D. Miklos Pharmacyclics, Pharma, Adaptive Biotechnologies, Novartis, BMS, Janssen Roche, Genentech, Precision Bioscience, Allogene, Miltenyi Biotec, Fate 2Seventy, Adicet Diehn AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Gritstone Oncology, Illumina, CiberMed, Varian Medical Systems, Illumina Frank Biotechnologies Roche/Genentech Kite/Gilead Kurtz Genentech diagnostics A. Alizadeh Employment leadership position: Celgene, Chugai, Gilead, Janssen, CiberMed Inc., Diagnostics, FortySeven Therapeutics. Pfizer