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Author Notes:

Correspondence: David Avigan, Hematologic Malignancies, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215. E-mail: davigan@bidmc.harvard.edu

Author contributions: D.J. Chung: Conceptualization, investigation, methodology, writing–original draft, writing–review and editing. N. Shah: Conceptualization, investigation, methodology, writing–original draft, writing–review and editing. J. Wu: Data curation, formal analysis, investigation, methodology, writing–original draft, writing–review and editing. B. Logan: Investigation, methodology, writing–review and editing. L. Bisharat: Investigation, methodology, writing–review and editing. N. Callander: Conceptualization, investigation, methodology, writing–original draft, writing–review and editing. G. Cheloni: Conceptualization, investigation, methodology, writing–original draft, writing–review and editing. K. Anderson: Investigation, methodology, writing–review and editing. T. Chodon: Investigation, methodology, writing–review and editing. B. Dhakal: Investigation, methodology, writing–review and editing. S. Devine: Investigation, methodology, writing–review and editing. P. Somaiya Dutt: Investigation, methodology, writing–review and editing. Y. Efebera: Investigation, methodology, writing–review and editing. N. Geller: Investigation, methodology, writing–review and editing. H. Ghiasuddin: Investigation, methodology, writing–review and editing. P. Hematti: Investigation, methodology, writing–review and editing. L. Holmberg: Investigation, methodology, writing–review and editing. A. Howard: Investigation, methodology, writing–review and editing. B. Johnson: Conceptualization, investigation, methodology, writing–original draft, writing–review and editing. D. Karagkouni: Conceptualization, investigation, methodology, writing–original draft, writing–review and editing. H.M. Lazarus: Investigation, methodology, writing–review and editing. E. Malek: Investigation, methodology, writing–review and editing. P. McCarthy: Investigation, methodology, writing–review and editing. D. McKenna: Investigation, methodology, writing–review and editing. A. Mendizabal: Investigation, methodology, writing–review and editing. A. Nooka: Investigation, methodology, writing–review and editing. N. Munshi: Investigation, methodology, writing–review and editing. L. O'Donnell: Investigation, methodology, writing–review and editing. A.P. Rapoport: Investigation, methodology, writing–review and editing. J. Reese: Investigation, methodology, writing–review and editing. J. Rosenblatt: Investigation, methodology, writing–review and editing. R. Soiffer: Investigation, methodology, writing–review and editing. D. Stroopinsky: Investigation, methodology, writing–review and editing. L. Uhl: Conceptualization, investigation, methodology, writing–original draft, writing–review and editing. I.S. Vlachos: Conceptualization, investigation, methodology, writing–original draft, writing–review and editing. E.K. Waller: Investigation, methodology, writing–review and editing. J.W. Young: Conceptualization, investigation, methodology, writing–original draft, writing–review and editing. M.C. Pasquini: Conceptualization, investigation, methodology, writing–original draft, writing–review and editing. D. Avigan: Conceptualization, data curation, formal analysis, investigation, methodology, writing–original draft, writing–review and editing.

Competing interests: N. Shah reports grants from Celgene/BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar, and Precision Biosciences, and other support from GSK, Amgen, Indapta Therapeutics, Sanofi, CareDx, Kite, Karyopharm, Oncopeptides, CSL Behring, Allogene, and AstraZeneca outside the submitted work. K. Anderson reports personal fees from Pfizer, AstraZeneca, and Janssen and other support from C4 Therapeutics, Dynamic Cell Therapies, Window Therapeutics, Starton Therapeutics, NextRNA, and Oncopep outside the submitted work. B. Dhakal reports grants and personal fees from Sanofi, Janssen, GSK, and BMS; personal fees from Genentech, Pfizer, Arcellx, and Karyopharm; and grants from Carsgen outside the submitted work. L. Holmberg reports grants from Seattle Genetics, Sanofi, Millennium-Takeda, Bristol-Myers Squibb, Merck, and Iteos outside the submitted work as well as royalties from UpToDate. H.M. Lazarus reports personal fees from Partner Therapeutics and Bristol-Myers Squibb outside the submitted work. E. Malek served on advisory boards for Takeda, Celgene, Janssen, Sanofi, Karyopharm, and Adaptive Biotechnology; is a speaker for Amgen, Takeda, Bristol-Myers Squibb, Karyopharm, and Adaptive Biotechnology; and received research funding from Medpacto Pharmaceuticals. P. McCarthy reports other support from Bristol-Myers Squibb, Janssen, Oncopeptides, Karyopharm, Starton, Partner Therapeutics, Takeda, BeiGene, HSC Acquisition, and GSK outside the submitted work. D. McKenna reports grants from NIH during the conduct of the study. A. Nooka reports personal fees from Adaptive Biotechnologies, Amgen, Beyond Spring, Bristol-Myers Squibb, Cellectar Biosciences, GlaxoSmithKline, Janssen, Karyopharm, Oncopeptides, ONK Therapeutics, Pfizer, Sanofi, Secura Bio, and Takeda outside the submitted work. N. Munshi reports personal fees from AbbVie, Adaptive, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Legend, Novartis, Pfizer, Takeda, and Dana-Farber Cancer Institute and personal fees and other support from OncoPep outside the submitted work. L. O'Donnell reports grants from NIH/NCI/BMTCTN during the conduct of the study. J. Rosenblatt reports grants from MMRF and Celgene during the conduct of the study as well as grants and other support from BMS; grants from Sanofi and Karyopharm; other support from Attivare, Parexel, Clario/Bioclinica, Amgen, Merck, Kite Pharma, Partner Tx, Imaging Endpoint, Dava Oncology, and Wolters Kluwer Health, Inc.; and grants and nonfinancial support from Celgene outside the submitted work. In addition, J. Rosenblatt has a patent for PCT/US2021059199 pending. R. Soiffer reports personal fees from BMS, Vor, Gilead, Astellas, Smart Immune, Cugene, Jasper, BlueSphere Bio, and Daiichi Sankyo outside the submitted work. D. Stroopinsky reports other support from Takeda Pharmaceuticals during the conduct of the study. I.S. Vlachos reports grants from NCI, NHLBI, Singular Genomics, Harvard Stem Cell Institute, and Massachusetts Life Sciences Center and personal fees from Mosaic, Guidepoint Global, and Next RNA and outside the submitted work. E.K. Waller reports grants from BMTCTN during the conduct of the study. M.C. Pasquini reports grants from Novartis, Kite Pharma, and Janssen and grants and personal fees from Bristol-Myers Squibb outside the submitted work. D. Avigan reports grants from MMRF and CTN (NIHLBI) during the conduct of the study as well as grants and other support from Celgene and Kite Pharma; grants from Pharmacyclics; and other support from Juno, Partners TX, Karyopharm, BMS, Aviv MedTech Ltd., Takeda, Legend Bio Tech, Chugai, Caribou Biosciences, Janssen, Parexel, Sanofi, and Kowa outside the submitted work. In addition, D. Avigan has as a patent for Personalized Cancer Vaccine and CAR T cells (PCT/US2021/059199) pending. No disclosures were reported by the other authors.

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Research Funding:

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:

  • dendritic cell
  • multiple myeloma
  • autologous hematopoietic cell transplant

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

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Journal Title:

Clinical Cancer Research

Volume:

Volume 29, Number 23

Publisher:

, Pages 4784-4796

Type of Work:

Article | Final Publisher PDF

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.

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©2023 The Authors; Published by the American Association for Cancer Research

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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