Elevated Axicabtagene Ciloleucel (CAR-19) Expansion By Immunophenotyping Is Associated with Toxicity in Diffuse Large B-Cell Lymphoma

摘要: Background: Axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR-T), showed significant clinical responses in patients with relapsed-refractory large-B cell lymphomas the Zuma-1 trial (Neelapu et al, NEJM 2017). analysis blood CAR-T expansion was associated response and toxicity. Herein, we report on 25 treated commercial axi-cel describe by immunophenotyping its correlation outcomes. Methods: Twenty-five aggressive lymphoma consecutively apheresed at Stanford University prior to June 30, 2018 were studied IRB approved biorepository-clinical outcome protocol. Cytokine release syndrome (CRS) graded Lee criteria (Blood 2014) neurotoxicity according Neelapu et. al (Nat. Rev. Clin. Onc. assessed peripheral flow cytometry days 7, 14, 21 28 then monthly. cells identified gating singlet+, live+, CD45+, CD14-, CD3+, anti-CD19-specific CAR mAb (clone 136.20.1; Jena Plos 2013) characterized as either CD4+ or CD8+. Results: Of patients, 3 died infusion due progressive lymphoma. 22 infused 14 (64%) would have been eligible for trial. Reasons ineligibility included symptomatic DVT (n=2), renal insufficiency (n=1), transaminitis thrombocytopenia MDS pleural effusion (n=1) 1 ineligible multiple criteria. Median time from initial clinic visit 47 (range 34-117); median apheresis 19-38). Nine received bridging therapy lymphodepletion chemotherapy (chemo = 4, radiation 2, high dose dexamethasone 3). Axi-cel occurred hospital followed expectantly a minimum of 7 until adverse events resolved Ninety-five percent developed CRS (Grade 2 73%, none ≥Grade number tocilizumab doses 0-4). Neurotoxicity 64%, Grade 4 27%. Corticosteroid required 82% (77% both steroids). duration steroids 8.5 1-30); 12 least week ≥2 weeks. infused, complete (CR) day 45% (ORR 86%). 15 evaluable months, ORR 53% (CR PR 1) 47% progressed, similar Zuma-1. Ineligibility not inferior Overall, peak vivo using anti-CAR19 38 CAR-T/ul (Fig. 1A), matching RT-PCR measured levels reported As shown Fig. 1A, majority Patients had significantly higher (both CD8+) compared those 0 1B). Grades 2-4 total CD8+ but Illustratively, most robust (▪, ▼ 1A) experienced including status epilepticus requiring anti-epileptics intubation. Peak did correlate CR 28; differ between who require steroids. Fine needle aspirates (FNA) subset FDG-avid lymph nodes 2-3 post within node despite low detectable circulating CAR-T. Figure 1C depicts 76-year-old male double expressor DLBCL attained below average (6 CAR-T/ul), while his FNA >35% CD3+ T-cells expressed CAR19. submission, 34 updated results will be presented. Conclusion: Our 86% 45%, 36% ineligibilities steroid use 82%. Blood response. Detection concentration affected suggests quantification disease sites could predictive responses. J.Y.S B.S are co-first authors Disclosures Latchford:Kite Gilead Company: Speakers Bureau. Muffly:Adaptive Biotechnologies: Research Funding; Shire Pharmaceuticals: Funding. Miklos:Kite - Gilead: Consultancy, Janssen: Genentech: Novartis: Pharmacyclics Abbot: Adaptive