| Title: |
Randomized Trial of a Personalized Dendritic Cell Vaccine after Autologous Stem Cell Transplant for Multiple Myeloma |
| Authors: |
Chung, David J; Shah, Nina; Wu, Juan; Logan, Brent; Bisharat, Lina; Callander, Natalie; Cheloni, Giulia; Anderson, Kenneth; Chodon, Thinle; Dhakal, Binod; Devine, Steve; Dutt, Poorvi Somaiya; 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 |
| Source: |
Clinical Cancer Research, vol 29, iss 23 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2023 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
32 Biomedical and Clinical Sciences (for-2020); 3204 Immunology (for-2020); Rare Diseases (rcdc); Clinical Trials and Supportive Activities (rcdc); Vaccine Related (rcdc); Stem Cell Research (rcdc); Clinical Research (rcdc); Transplantation (rcdc); Cancer (rcdc); Biotechnology (rcdc); Orphan Drug (rcdc); Health Disparities (rcdc); Hematology (rcdc); Stem Cell Research - Nonembryonic - Human (rcdc); Prevention (rcdc); Immunization (rcdc); Regenerative Medicine (rcdc); 3.4 Vaccines (hrcs-rac); Cancer (hrcs-hc); 3 Good Health and Well Being (sdg); Humans (mesh); Multiple Myeloma (mesh); Lenalidomide (mesh); Granulocyte-Macrophage Colony-Stimulating Factor (mesh); Hematopoietic Stem Cell Transplantation (mesh); Transplantation; Autologous (mesh); Dendritic Cells (mesh); Antineoplastic Combined Chemotherapy Protocols (mesh); Dexamethasone (mesh) |
| Time: |
4784 - 4796 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt09h840ks; https://escholarship.org/uc/item/09h840ks; https://escholarship.org/content/qt09h840ks/qt09h840ks.pdf |
| DOI: |
10.1158/1078-0432.ccr-23-0235 |
| Availability: |
https://escholarship.org/uc/item/09h840ks; https://escholarship.org/content/qt09h840ks/qt09h840ks.pdf; https://doi.org/10.1158/1078-0432.ccr-23-0235 |
| Rights: |
CC-BY-NC-ND |
| Accession Number: |
edsbas.FB11B3E3 |
| Database: |
BASE |