Prognostic Value of Minimal Residual Disease (MRD) Among Patients with Classical Hodgkin Lymphoma Undergoing Autologous Stem Cell Transplantation

Background: Autologous stem cell transplantation (ASCT) can be curative for a subset of patients (pts) with relapsed/refractory classical Hodgkin lymphoma (cHL). Post-ASCT maintenance therapy with brentuximab vedotin (BV) improves progression-free survival (PFS) among pts with high-risk clinical features, and PD-1 blockade is also being investigated in this setting. Ideally, novel biomarkers could be used to guide pt selection for these post-ASCT therapies. We hypothesized that the presence of minimal residual disease (MRD), quantified using immunoglobulin-based next generation sequencing (IgNGS), could predict post-ASCT relapse. As a preliminary test of this hypothesis, we analyzed a cohort of cHL pts who had serial peripheral blood mononuclear cell (PBMC) and plasma samples collected before or after ASCT. Methods: Samples from 2 cohorts (n=36) were analyzed. 28 pts were prospectively enrolled on a biobanking protocol and underwent ASCT at Dana-Farber Cancer Institute between 2014-2016 (biobank cohort). In addition, 8 pts underwent ASCT between 2015 and 2016 and subsequently participated in a multicenter phase II trial of post-ASCT pembrolizumab maintenance (PM) (trial cohort) (Armand, Blood 2020). Tumor tissue and serial post-ASCT plasma and PBMC samples were collected for all pts, and some pts also had pre-ASCT PB samples available for analysis. NGS of Ig receptor sequences (IgNGS) (clonoSEQ Ò, Adaptive Biotechnologies) was used to identify and track tumor clonotypes, as previously described (Ching, BMC Cancer 2020). MRD testing was not used for clinical decision making. Results: The 36 enrolled pts received a median of 2 lines of therapy, and 30 pts (83%) achieved a complete response (CR) on pre-ASCT positron emission tomography (PET). In total, 19 pts received post-ASCT treatment - PM (n=8, all on trial), radiation therapy (n=5), BV maintenance (n=4), and allogeneic stem cell transplantation as part of a planned tandem transplant (n=2). Among 36 enrolled pts, 12 (33%) had an identifiable clonotype (11/28 biobank and 1/8 trial). Higher rates of clonotype detection were seen in pts aged