Document Type
Article
Publication Title
Clinical cancer research : an official journal of the American Association for Cancer Research
Abstract
PURPOSE: Vaccination with dendritic cell (DC)/multiple myeloma (MM) fusions has been shown to induce the expansion of circulating multiple myeloma-reactive lymphocytes and consolidation of clinical response following autologous hematopoietic cell transplant (auto-HCT).
PATIENTS AND METHODS: In this randomized phase II trial (NCT02728102), we assessed the effect of DC/MM fusion vaccination, GM-CSF, and lenalidomide maintenance as compared with control arms of GM-CSF and lenalidomide or lenalidomide maintenance alone on clinical response rates and induction of multiple myeloma-specific immunity at 1-year posttransplant.
RESULTS: The study enrolled 203 patients, with 140 randomized posttransplantation. Vaccine production was successful in 63 of 68 patients. At 1 year, rates of CR were 52.9% (vaccine) and 50% (control; P = 0.37, 80% CI 44.5%, 61.3%, and 41.6%, 58.4%, respectively), and rates of VGPR or better were 85.3% (vaccine) and 77.8% (control; P = 0.2). Conversion to CR at 1 year was 34.8% (vaccine) and 27.3% (control; P = 0.4). Vaccination induced a statistically significant expansion of multiple myeloma-reactive T cells at 1 year compared with before vaccination (P = 0.024) and in contrast to the nonvaccine arm (P = 0.026). Single-cell transcriptomics revealed clonotypic expansion of activated CD8 cells and shared dominant clonotypes between patients at 1-year posttransplant.
CONCLUSIONS: DC/MM fusion vaccination with lenalidomide did not result in a statistically significant increase in CR rates at 1 year posttransplant but was associated with a significant increase in circulating multiple myeloma-reactive lymphocytes indicative of tumor-specific immunity. Site-specific production of a personalized cell therapy with centralized product characterization was effectively accomplished in the context of a multicenter cooperative group study. See related commentary by Qazilbash and Kwak, p. 4703.
First Page
4784
Last Page
4796
DOI
10.1158/1078-0432.CCR-23-0235
Publication Date
12-1-2023
Recommended Citation
Chung, David J; Shah, Nina; Wu, Juan; Logan, Brent; Bisharat, Lina; Callander, Natalie; Cheloni, Giulia; Anderson, Kenneth; Chodon, Thinle; Dhakal, Binod; Devine, Steve; Somaiya Dutt, Poorvi; Efebera, Yvonne; Geller, Nancy; Ghiasuddin, Haider; Hematti, Peiman; Holmberg, Leona; Howard, Alan; Johnson, Bryon; Karagkouni, Dimitra; Lazarus, Hillard M; Malek, Ehsan; McCarthy, Philip; McKenna, David; Mendizabal, Adam; Nooka, Ajay; Munshi, Nikhil; O'Donnell, Lynn; Rapoport, Aaron P; Reese, Jane; Rosenblatt, Jacalyn; Soiffer, Robert; Stroopinsky, Dina; Uhl, Lynne; Vlachos, Ioannis S; Waller, Edmund K; Young, James W; Pasquini, Marcelo C; and Avigan, David, "Randomized Phase II Trial of Dendritic Cell/Myeloma Fusion Vaccine with Lenalidomide Maintenance after Upfront Autologous Hematopoietic Cell Transplantation for Multiple Myeloma: BMT CTN 1401." (2023). Oncology Articles. 16.
https://scholarlyworks.ohiohealth.com/oncology-articles/16