Abstract 6785: Dendritic cell/myeloma fusion vaccine with lenalidomide maintenance following autologous hematopoietic cell transplant induced T cell activation and expansion

Abstract

Abstract Introduction: Multiple myeloma (MM), a clonal disorder of terminally differentiated plasma cells, is the second most common hematologic malignancy with ~57.9% 5-year survival rate. Current MM therapies are not curative and in most patients MM relapse. Aiming to restore antitumor immunity and counteract MM evolution, we have developed a personalized dendritic(DC)/MM cell fusion vaccine, whereby several tumor antigens are presented in the context of DC mediated co-stimulation. BMT CTN 1401 is a multicenter randomized phase II clinical trial (NCT02728102) evaluating the efficacy of the DC/MM vaccine combined with lenalidomide maintenance (Len) after autoHCT. 203 patients were enrolled from 18 centers. Aim: To evaluate the impact of the DC/MM vaccine on the establishment of anti-MM immune response we profiled the peripheral blood (PB) immune landscape at the single-cell level, with particular focus on the T cell compartment. Method: We performed single-cell immunoprofiling (gene expression + V(D)J sequencing) on 40 patients (3xDC/MM vaccine/Len/GM-CSF: N=20; Len/GM-CSF: N=10; Len: N=10). 160 PB mononuclear cells (PBMC) samples were collected at enrollment, prior to Len, after 1 and 3 vaccines and were processed using the 10x Genomics single cell 5' assay. Here we present the analysis relative to 52 PBMC samples from 13 vaccinated patients included in the initial study cohort. The remaining 108 PBMC samples have already been subjected to single-cell immunoprofiling and the analysis is ongoing. Results: 309,423 cells passed quality-check identifying 47 cell populations, corresponding to 20 major compartments. The T cell compartment (146,373 cells) was divided into 14 different cell populations including activated CD8, CD4, and NKT cells that exhibited a gradual increase during the course of the study. Relatively, TCR sequencing demonstrated a recovery of T cell clonal diversity and a progressive rise in the frequency of expanded clonotypes within the activated CD4 and cytotoxic T cell populations after vaccination. Consistently, we observed a progressively raised number of shared TCR clonotypes within the activated CD8 and CD4 T cell subsets. The identification of common epitope/paratope hotspots among the expanded clonotypes and the different patients revealed a higher proportion of shared TCR clonotype groups across patients after vaccination compared to the early post-transplant period, predominantly after 3 vaccinations. Conclusions: Assessment of PBMC samples from 13 vaccinated patients provided a detailed picture of the PBMC landscape. The constant T cell expansion in patients following vaccination coupled with the shared paratope/epitope hotspots and TCR signatures among patients indicated the TCR cross-reactivity and suggested for the establishment of an anti-MM immune response. Citation Format: Giulia Cheloni, Dimitra Karagkouni, Daniela Torres, David J. Chung, Nina Shah, Natalie S. Callander, Thinle Chodon, Yvonne Efebera, Nancy Geller, Peiman Hematti, Hillard Lazarus, Ehsan Malek, Philip L. McCarthy, Ajay K. Nooka, Jacalyn Rosenblatt, Aaron P. Rapoport, Robert J. Soiffer, Dina Stroopinsky, Edmund K. Waller, Marcelo C. Pasquini, Ioannis Vlachos, David Avigan. Dendritic cell/myeloma fusion vaccine with lenalidomide maintenance following autologous hematopoietic cell transplant induced T cell activation and expansion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6785.