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

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). In this randomized phase II trial (NCT0...

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Vydané v:	Clinical cancer research Ročník 29; číslo 23; s. 4784
Hlavní autori:	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, Avigan, David
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 01.12.2023
Predmet:	Antineoplastic Combined Chemotherapy Protocols - adverse effects Dendritic Cells Dexamethasone - therapeutic use Granulocyte-Macrophage Colony-Stimulating Factor - genetics Hematopoietic Stem Cell Transplantation Humans Lenalidomide - therapeutic use Multiple Myeloma - drug therapy Transplantation, Autologous
ISSN:	1557-3265, 1557-3265
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Popis
Shrnutí:	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). 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. 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. 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.
Bibliografia:	SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-Undefined-1 content type line 23 ObjectType-Article-3
ISSN:	1557-3265 1557-3265
DOI:	10.1158/1078-0432.CCR-23-0235