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

• Type of Material: Article
• Authors: David J. Chung, Memorial Sloan Kettering Cancer Center; Nina Shah, University of California San Francisco; Juan Wu, Emmes Company; Brent Logan, Medical College of Wisconsin; Lina Bisharat, Beth Israel Deaconess Medical Center; Natalie Callander, University of Wisconsin; Giulia Cheloni, Beth Israel Deaconess Medical Center; Kenneth Anderson, Dana Farber Cancer Institute; Thinle Chodon, Roswell Park Cancer Institute; Binod dhakal, Medical College of Wisconsin; Steve Decine, National Marrow Donor Program; Poorvi Somaiya Dutt, Beth Israel Deaconess Medical Center; Yvonne Efebera, OhioHealth; Nancy Geller, Heart and Blood Institute; Haider Ghiasuddin, Beth Israel Deaconess Medical Center; Peiman Hematti, University of Wisconsin; Leona Holmberg, Fred Hutchinson Cancer Research Center; Alan Howard, Medical College of Wisconsin; Bryon Johnson, Medical College of Wisconsin; Dimitra Karagkouni, Beth Israel Deaconess Medical Center; Hillard M. Lazarus, Case Western Reserve University; Ehsan Malek, Case Western Reserve University; Philip McCarthy, Roswell Park Cancer Institute; David McKenna, University of Minnesota; Adam Mendizabal, Emmes Company; Ajay Nooka, Emory University; Nikhil Munshi, Dana Farber Cancer Institute; Lynn O'Donnell, Ohio State University; Aaron P. Rapoport, University of Maryland, Baltimore; Jane Reese, Case Western Reserve University; Jacalyn Rosenblatt, Beth Israel Deaconess Medical Center; Robert Soiffer, Dana Farber Cancer Institute; Dina Stroopinksy, Beth Israel Deaconess Medical Center; Lynne Uhl, Beth Israel Deaconess Medical Center; Ioannis S. Vlachos, Beth Israel Deaconess Medical Center; Edmund K Waller, Emory University; James W. Young, Memorial Sloan Kettering Cancer Center; Marcelo C. Pasquini, Medical College of Wisconsin; David Avigan, Beth Israel Deaconess Medical Center
• Language: English
• Date: 2023-07-18
• Publisher: American Association for Cancer Research
• Publication Version: Final Published Version
• Copyright Statement: ©2023 The Authors; Published by the American Association for Cancer Research
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): https://doi.org/10.1158/1078-0432.CCR-23-0235
• Title of Journal or Parent Work: Clinical Cancer Research
• Volume: 29
• Issue: 23
• Start Page: 4784
• End Page: 4796
• Grant/Funding Information: Support for this study was provided by grants #U10HL069294 and #U24HL138660 to the Blood and Marrow Transplant Clinical Trials Network from the National Heart, Lung, and Blood Institute and the National Cancer Institute along with contributions by Celgene Corporation and the Multiple Myeloma Research Fund.; The publication costs of this article were defrayed in part by the payment of publication fees. Therefore, and solely to indicate this fact, this article is hereby marked “advertisement” in accordance with 18 USC section 1734.
• Keywords: autologous hematopoietic cell transplant; dendritic cell; multiple myeloma
• Research Categories: Health Sciences, Immunology; Biology, Cell

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.