Prognostic Value of Circulating Tumor DNA (ctDNA) in Autologous Stem Cell Graft and Post-Transplant Plasma Samples Among Patients with Diffuse Large B-Cell Lymphoma

Background: While autologous stem cell transplantation (ASCT) can be curative for patients (pts) with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), relapse remains common. With the emergence of novel effective therapies, it is even more important to identify pts at high risk of treatment failure who may not benefit from ASCT, and pts with impending post-ASCT relapse who may be candidates for pre-emptive interventions. We assembled cohorts of DLBCL pts who underwent ASCT and had apheresis stem cell (ASC) samples or serially collected post-ASCT peripheral blood mononuclear cell (PBMC) and plasma samples. We hypothesized that circulating tumor DNA (ctDNA) identified using immunoglobulin-based next generation sequencing (IgNGS) in ASC or PB samples could predict relapse. Methods: Samples from 3 cohorts were analyzed. Pts in cohort 1 (C1) underwent ASCT at Dana-Farber Cancer Institute (DFCI) from 2003-2013 (Herrera, ASH 2015). Archival tumor tissue and ASC samples were retrospectively collected for analysis. Pts in cohort 2 (C2) were prospectively enrolled on a banking protocol at DFCI and underwent ASCT from 2014-2016. Pts in cohort 3 (C3) underwent ASCT from 2015-2016 and participated in a multicenter phase II trial of post-ASCT pembrolizumab maintenance (PM) (Frigault, Blood Adv 2020). Pts in C2/C3 had tumor tissue and serially collected post-ASCT PBMC and plasma samples as mandated by protocol, and a subset had available pre-ASCT PB or ASC samples. Because PM did not demonstrate a clear benefit in the trial, all cohorts were analyzed together. IgNGS (Adaptive Biotechnologies; Seattle, WA) was performed, as previously described (Armand, BJH 2013). In all cases, ctDNA testing was not performed in real-time or used to drive clinical decisions. Results: 152 pts were enrolled. Among 141 pts with sufficient DNA for testing, a clonotype was identified in 112 (78%) with a higher detection rate in more recent cohorts - C2 (93%) and C3 (90%) vs C1 (67%). Among 97 pts with an available ASC sample, 23 (24%) were ctDNA-positive (pos). With a median follow-up among survivors of 69 months (m) (range 13-185), the 5-year (y) progression-free survival (PFS) for ASC ctDNA-pos and ASC ctDNA-negative (neg) pts were 13% (95% CI 3-30%) and 52% (95% CI 40-63%), respectively (HR 2.8, p