Circulating tumor DNA (ctDNA) by clonoSEQ to monitor residual disease after axicabtagene ciloleucel (axi‐cel) in large B‐cell lymphoma (LBCL)

Introduction: Most patients (pts) with LBCL respond to axi-cel, but many will eventually experience disease progression (Jacobson et al. JCO. 2020). Monitoring of ctDNA from blood, a minimally invasive diagnostic tool, has been used assess measurable residual (MRD) prognostic value, including in pts diffuse treated axi-cel the third line therapy (3L; Frank 2019). Here, we explored value predict outcomes after across lines treatment. Methods: Pts ZUMA-12 (Phase 2 1L), ZUMA-7 3 or standard care [SOC] 2L), and ZUMA-14 + rituximab 3L) were included. All studies included initial MRD testing ≈30 days post infusion. ClonoSEQ assay (limit detection ≈0.0001%–0.00001%) was define lymphoma B-cell clonotype formalin-fixed, paraffin-embedded (FFPE) biopsy tissue prior infusion track blood Positive predictive (PPV; MRD+ who relapsed nonresponders/total ×100) negative (NPV; MRD- ongoing response/total assessed at Day 28, Month (Mo) 3, Mo 5 for 3L; Days 50, 100, 150, 9, 24 2L; 6 1L. Results: In 3L, PPV 28 88% (7/8) NPV 83% (10/12). remained (10/12) increased 100% (8/8) 5. Overall, (5/6) had detected any time; those 5, (5/5) time median 43 progression. 2L, rate among evaluable pre-infusion samples only 69% (11/16). At (7/7) SOC arm, whereas it 57% (4/7) arm. over reaching by 9 (2/2). 53% (8/15) arm 38% (5/13) 47% (9/19) on 78% (7/9) 35 1L, most (11/14) response data cut off. The 50% (1/2): two detectable one subsequently became yet just while second up 24. (7/8). Conclusions: assessment clonoSEQ varied axi-cel. A relatively high undetectable baseline 2L setting relapse 1L settings warrants exploration more sensitive monitoring methods. Encore Abstract - previously submitted ASCO 2023 research funded by: Kite, Gilead Company Keywords: Aggressive non-Hodgkin lymphoma, Cellular therapies, Diagnostic Prognostic Biomarkers Conflicts interests pertinent abstract. B. R. Miles Employment leadership position: Stock ownership: S. Vardhanabhuti C. To Sciences M. Schupp Shahani H. Xu J. L. Munoz Consultant advisory role: Pharmacyclics/Abbvie, Bayer, Gilead/Kite Pharma, Pfizer, Janssen, Juno/Celgene, BMS, Kyowa, Alexion, Fosunkite, Innovent, Seattle Genetics, Debiopharm, Karyopharm, Genmab, ADC Therapeutics, Epizyme, Beigene, Servier, Novartis, Morphosys/Incyte, Secura Bio, TG MEI, Lilly/Loxo Honoraria: Targeted Oncology, OncView, Curio, Physicians' Education Resource, Genetics Research funding: Celgene, Merck, Portola, Incyte, Genentech, Pharmacyclics, Millennium Other remuneration: Pharmacyclics/Janssen, Acrotech/Aurobindo, Verastem, AstraZeneca, Celgene/BMS, Genentech/Roche Westin Bristol-Myers Squibb, Gilead, Company, MonteRosa, Umoja Novartis Shen Company; Atara Filosto Kite Patents, royalties, other intellectual property Tusk Therapeutics.