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.
Humans
Multiple Myeloma
/ drug therapy
Lenalidomide
/ therapeutic use
Granulocyte-Macrophage Colony-Stimulating Factor
/ genetics
Hematopoietic Stem Cell Transplantation
Transplantation, Autologous
Dendritic Cells
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Dexamethasone
/ therapeutic use
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 Dec 2023
01 Dec 2023
Historique:
received:
02
02
2023
revised:
28
03
2023
accepted:
12
07
2023
medline:
4
12
2023
pubmed:
18
7
2023
entrez:
18
7
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37463058
pii: 727837
doi: 10.1158/1078-0432.CCR-23-0235
pmc: PMC10690096
doi:
Substances chimiques
Lenalidomide
F0P408N6V4
Granulocyte-Macrophage Colony-Stimulating Factor
83869-56-1
Dexamethasone
7S5I7G3JQL
Types de publication
Randomized Controlled Trial
Clinical Trial, Phase II
Multicenter Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4784-4796Subventions
Organisme : NHLBI NIH HHS
ID : U10 HL069294
Pays : United States
Organisme : NHLBI NIH HHS
ID : U24 HL138660
Pays : United States
Informations de copyright
©2023 The Authors; Published by the American Association for Cancer Research.
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