Monitoring ctDNA in r/r DLBCL patients following the CAR T-cell therapy axicabtagene ciloleucel: Day 28 landmark analysis.

• DOI: 10.1200/jco.2019.37.15_suppl.7552
• Publication Date: 2020-03-12T16:18:58Z
• Authors: Matthew Joshua Frank; Nasheed M. Hossain; Ali Abbas Bukhari; Erin Dean; Jay Y. Spiegel; Gursharan K. Claire; Ilan Kirsch; Allison Jacob; Chelsea D. Mullins; Lik Wee Lee; Katherine A. Kong; Juliana K. Craig; Crystal Mackall; Aaron Rapoport; Saurabh Dahiya; Frederick Lundry ...; David Bernard Miklos
• Keywords: Minimal Residual Disease; Refractory (planetary science); Circulating tumor DNA

7552 Background: Axicabtagene Ciloleucel (Axi-cel) is an autologous anti-CD19 CAR T-cell therapy approved for the treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). Long‐term analysis Zuma‐1 clinical trial showed ~40% patients remained progression-free at 2 years (Locke, Lancet Oncology 2018). Early identification who will later progress after T cell may improve care and patient outcomes. Methods: As 2/1/2019, we enrolled 50 on a multi-institutional, prospective study measuring circulating tumor DNA(ctDNA) minimal residual disease (MRD) in r/r DLBCL undergoing with Axi-cel. Using next generation sequencing-MRD assay (Adaptive Biotechnologies; Seattle WA), ctDNA levels were measured pre, 0, 7, 14, 21, 28, 56, 90, 180, 270, 365 days following Axi-cel infusion. A pre-planned comparison between EDTA, Streck, CFD tubes initial 10 determined tube provided optimal analyte stability over 144 hours sample collection. are being used to collect all samples. Results: 24 subjects have 3 or more months follow up their MRD significantly associated day 28 landmark shows 12 negative positive as defined by detection none any tumor-associated ctDNA, respectively. MRD+ subsequently developed progressive disease. In contrast, only MRD- progressed other remain CR. (p = 0.0033, Fisher's exact test). With median 237 days, PFS infusion vs. 93 not reach, p 0.0010 Log-rank test. Median OS 281 0.0399 Conclusions: After infusion, ctDNA-based associates identified early at-risk prior progression. These results provide rationale designing MRD-based risk-adaptive trials.