Association of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination With Extension of Survival Among Patients With Newly Diagnosed and Recurrent Glioblastoma
Year: 2022
Type: article
Abstract: Importance: Glioblastoma is the most lethal primary brain cancer. Clinical outcomes for glioblastoma remain poor, and new treatments are needed. Objective: To investigate whether adding autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L) to standard of care (SOC) extends survival among patients with glioblastoma. Design, Setting, and Participants: This phase 3, prospective, externally controlled nonrandomized trial compared overall survival (OS) in patients with newly diagnosed glioblastoma (nGBM) and recurrent glioblastoma (rGBM) treated with DCVax-L plus SOC vs contemporaneous matched external control patients treated with SOC. This international, multicenter trial was conducted at 94 sites in 4 countries from August 2007 to November 2015. Data analysis was conducted from October 2020 to September 2021. Interventions: The active treatment was DCVax-L plus SOC temozolomide. The nGBM external control patients received SOC temozolomide and placebo; the rGBM external controls received approved rGBM therapies. Main Outcomes and Measures: The primary and secondary end points compared overall survival (OS) in nGBM and rGBM, respectively, with contemporaneous matched external control populations from the control groups of other formal randomized clinical trials. Results: A total of 331 patients were enrolled in the trial, with 232 randomized to the DCVax-L group and 99 to the placebo group. Median OS (mOS) for the 232 patients with nGBM receiving DCVax-L was 19.3 (95% CI, 17.5-21.3) months from randomization (22.4 months from surgery) vs 16.5 (95% CI, 16.0-17.5) months from randomization in control patients (HR = 0.80; 98% CI, 0.00-0.94; P = .002). Survival at 48 months from randomization was 15.7% vs 9.9%, and at 60 months, it was 13.0% vs 5.7%. For 64 patients with rGBM receiving DCVax-L, mOS was 13.2 (95% CI, 9.7-16.8) months from relapse vs 7.8 (95% CI, 7.2-8.2) months among control patients (HR, 0.58; 98% CI, 0.00-0.76; P < .001). Survival at 24 and 30 months after recurrence was 20.7% vs 9.6% and 11.1% vs 5.1%, respectively. Survival was improved in patients with nGBM with methylated MGMT receiving DCVax-L compared with external control patients (HR, 0.74; 98% CI, 0.55-1.00; P = .03). Conclusions and Relevance: In this study, adding DCVax-L to SOC resulted in clinically meaningful and statistically significant extension of survival for patients with both nGBM and rGBM compared with contemporaneous, matched external controls who received SOC alone. Trial Registration: ClinicalTrials.gov Identifier: NCT00045968.
Source: JAMA Oncology
Authors: Linda M. Liau, Keyoumars Ashkan, Steven Brem, Jian L. Campian, John E. Trusheim, Fabio M. Iwamoto, David D. Tran, George Ansstas, Charles S. Cobbs, Jason A. Heth, Michael E. Salacz, Stacy D’Andre, Robert D. Aiken, Yaron A. Moshel, Joo Y. Nam, Clement P. Pillainayagam, Stephanie A. Wagner, Kevin A. Walter, Rekha Chaudhary, Samuel A. Goldlust, Ian Y. Lee, Daniela A. Bota, Heinrich Elinzano, Jai Grewal, Kevin Lillehei, Tom Mikkelsen, Tobias Walbert, Steven Abram, Andrew J. Brenner, Matthew G. Ewend, Simon Khagi, Darren S. Lovick, Jana Portnow, Lyndon Kim, William G. Loudon, Nina L. Martinez, Reid C. Thompson, David E. Avigan, Karen L. Fink, Francois J. Geoffroy, Pierre Giglio, Oleg Gligich, Dietmar Krex, Scott M. Lindhorst, Jose Lutzky, Hans-Jörg Meisel, Minou Nadji-Ohl, Lhagva Sanchin, Andrew Sloan, Lynne P. Taylor, Julian K. Wu, Erin M. Dunbar, Arnold B. Etame, Santosh Kesari, David Mathieu, David E. Piccioni, David S. Baskin, Michel Lacroix, Sven-Axel May, Pamela Z. New, Timothy J. Pluard, Steven A. Toms, Victor Tse, Scott Peak, John L. Villano, James D. Battiste, Paul J. Mulholland, Michael L. Pearlman, Kevin Petrecca, Michael Schulder, Robert M. Prins, Alton L. Boynton, Marnix L. Bosch
Institutions: University of California, Los Angeles, King's College Hospital, University of Pennsylvania, Washington University in St. Louis, Abbott Northwestern Hospital, NewYork–Presbyterian Hospital, Columbia University Irving Medical Center, University of Florida Health, University of Florida, Swedish Medical Center, University of Michigan, Rutgers Cancer Institute, Sutter Health, Atlantic Health System, Rush University Medical Center, Rush University, The Ohio State University, Columbus Regional Healthcare System, University of Rochester, University of Cincinnati, Hackensack University Medical Center, Henry Ford Health, Henry Ford Hospital, University of California, Irvine, Rhode Island Hospital, Neurological Surgery, University of Colorado Boulder, University of Colorado Health, Saint Thomas Health, Mays Cancer Center at UT Health San Antonio, University of North Carolina at Chapel Hill, University of North Carolina Health Care, Dartmouth College, City Of Hope National Medical Center, City of Hope, Icahn School of Medicine at Mount Sinai, St. Joseph Hospital, Thomas Jefferson University, Jefferson Hospital for Neuroscience, Vanderbilt University, Vanderbilt University Medical Center, Beth Israel Deaconess Medical Center, Harvard University, Baylor Scott & White Health, Illinois CancerCare, Medical University of South Carolina, Mount Sinai Medical Center, MUSC Hollings Cancer Center, University of Miami, Sylvester Comprehensive Cancer Center, BG Klinikum Bergmannstrost Halle, Katharinenhospital, Klinikum Stuttgart, University Hospitals of Cleveland, University Hospitals Cleveland Medical Center, University Hospitals Seidman Cancer Center, Tufts Medical Center, Moffitt Cancer Center, Saint John's Health Center, Université de Sherbrooke, Centre Hospitalier Universitaire de Sherbrooke, Moores Cancer Center, Houston Methodist, Geisinger Neuroscience Institute, Klinikum Chemnitz, Baptist Health System, Saint Luke's Hospital, Brown University, Kaiser Permanente, Kaiser Permanente Redwood City Medical Center, University of Kentucky, Markey Cancer Center, OU Health, University of Oklahoma Health Sciences Center, University College Hospital, University College London, Montreal Neurological Institute and Hospital, McGill University, Hofstra University, Northwest Biotherapeutics (United States)
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: Kaiser Permanente, Brown University, University of Miami, Tufts Medical Center, McGill University, University of South Carolina, Moffitt Cancer Center, Université de Sherbrooke, Houston Methodist Hospital, Sylvester Comprehensive Cancer Center, University of Miami Health Systems, Northwell Health, Saint Luke's Health System, University College London, Hollings Cancer Center, Medical University of South Carolina, University of California, Los Angeles, University of California, San Diego, Montreal Neurological Institute and Hospital, Houston Methodist Research Institute, National Cancer Institute
OpenAlex ID: W4309183974