Association of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination With Extension of Survival Among Patients With Newly Diagnosed and Recurrent Glioblastoma
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- Linda M. Liau
- Department of Neurosurgery, University of California, Los Angeles
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- Keyoumars Ashkan
- King’s College Hospital, London, United Kingdom
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- Steven Brem
- Department of Neurosurgery, Penn Brain Tumor Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia
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- Jian L. Campian
- Division of Neurology, Washington University School of Medicine in St Louis, St Louis, Missouri
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- John E. Trusheim
- Givens Brain Tumor Center, Abbott Northwestern Hospital, Minneapolis, Minnesota
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- Fabio M. Iwamoto
- Columbia University Irving Medical Center, New York, New York
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- David D. Tran
- Preston A. Wells, Jr. Center for Brain Tumor Therapy, Division of Neuro-Oncology, Lillian S. Wells Department of Neurosurgery, University of Florida College of Medicine, Gainesville
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- George Ansstas
- Department of Neurological Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri
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- Charles S. Cobbs
- Ben and Catherine Ivy Center for Advanced Brain Tumor Treatment, Swedish Medical Center, Seattle, Washington
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- Jason A. Heth
- Taubman Medical Center, University of Michigan, Ann Arbor
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- Michael E. Salacz
- Neuro-Oncology Program, Rutgers Cancer Institute of New Jersey, New Brunswick
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- Stacy D’Andre
- Sutter Health, Sacramento, California
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- Robert D. Aiken
- Glasser Brain Tumor Center, Atlantic Healthcare, Summit, New Jersey
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- Yaron A. Moshel
- Glasser Brain Tumor Center, Atlantic Healthcare, Summit, New Jersey
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- Joo Y. Nam
- Department of Neurological Sciences, Rush Medical College, Chicago, Illinois
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- Clement P. Pillainayagam
- Department of Neurology, The Ohio State University, Columbus
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- Stephanie A. Wagner
- The Cancer Center of Columbus Regional Health, Columbus, Indiana
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- Kevin A. Walter
- University of Rochester, Rochester, New York
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- Rekha Chaudhary
- University of Cincinnati, Cincinnati, Ohio
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- Samuel A. Goldlust
- John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, New Jersey
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- Ian Y. Lee
- Department of Neurosurgery, Henry Ford Health System, Detroit, Michigan
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- Daniela A. Bota
- Department of Neurology and Chao Family Comprehensive Cancer Center, University of California, Irvine
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- Heinrich Elinzano
- Rhode Island Hospital, Providence
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- Jai Grewal
- Long Island Brain Tumor Center at NSPC, Lake Success, New York
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- Kevin Lillehei
- Department of Neurosurgery, University of Colorado Health Sciences Center, Boulder
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- Tom Mikkelsen
- Department of Neurosurgery, Henry Ford Health System, Detroit, Michigan
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- Tobias Walbert
- Department of Neurosurgery, Henry Ford Health System, Detroit, Michigan
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- Steven Abram
- Ascension St Thomas Brain and Spine Tumor Center, Howell Allen Clinic, Nashville, Tennessee
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- Andrew J. Brenner
- Mays Cancer Center at UT Health San Antonio, San Antonio, Texas
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- Matthew G. Ewend
- Department of Neurosurgery, UNC School of Medicine and UNC Health, Chapel Hill, North Carolina
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- Simon Khagi
- The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire
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- Darren S. Lovick
- Advent Health, Kansas City, Kansas
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- Jana Portnow
- Department of Medical Oncology & Therapeutics Research, City of Hope, Duarte, California
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- Lyndon Kim
- Division of Neuro-Oncology, Icahn School of Medicine at Mount Sinai, New York, New York
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- William G. Loudon
- Saint Joseph’s Hospital, Orange, California
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- Nina L. Martinez
- Jefferson Hospital for Neurosciences, Jefferson University, Philadelphia, Pennsylvania
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- Reid C. Thompson
- Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
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- David E. Avigan
- Beth Israel Deaconess Medical Center, Harvard Medical School, Cambridge, Massachusetts
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- Karen L. Fink
- Baylor Scott & White Neuro-Oncology Associates, Dallas, Texas
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- Francois J. Geoffroy
- Illinois Cancer Care, Galesburg, Peoria
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- Pierre Giglio
- Medical University of South Carolina Neurosciences, Charleston
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- Oleg Gligich
- Mount Sinai Medical Center, Miami Beach, Florida
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- Dietmar Krex
- Uniklinikum Dresden, Dresden, Germany
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- Scott M. Lindhorst
- Hollings Cancer Center, Medical University of South Carolina, Charleston
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- Jose Lutzky
- Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida
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- Hans-Jörg Meisel
- BG Klinikum Bergmannstrost, Halle, Germany
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- Minou Nadji-Ohl
- Neurochirurgie Katharinenhospital, Klinikum der Landeshauptstadt Stuttgart, Stuttgart, Germany
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- Lhagva Sanchin
- BG Klinikum Bergmannstrost, Halle, Germany
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- Andrew Sloan
- Seidman Cancer Center, University Hospitals–Cleveland Medical Center, Cleveland, Ohio
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- Lynne P. Taylor
- Department of Neurosurgery, Tufts Medical Center, Boston, Massachusetts
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- Julian K. Wu
- Department of Neurosurgery, Tufts Medical Center, Boston, Massachusetts
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- Erin M. Dunbar
- Piedmont Physicians Neuro-Oncology, Piedmont Brain Tumor Center, Atlanta, Georgia
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- Arnold B. Etame
- Department of Neuro-Oncology, Moffitt Cancer Center
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- Santosh Kesari
- Pacific Neurosciences Institute and Saint John’s Cancer Institute, Santa Monica, California
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- David Mathieu
- Centre de Recherche du CHUS, Université de Sherbrooke, Sherbrooke, Quebec, Canada
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- David E. Piccioni
- UC San Diego Moore’s Cancer Center, La Jolla, California
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- David S. Baskin
- Department of Neurosurgery, Houston Methodist Hospital, Houston, Texas
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- Michel Lacroix
- Geisinger Neuroscience Institute, Danville, Pennsylvania
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- Sven-Axel May
- Klinik für Neurochirurgie, Chemnitz, Germany
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- Pamela Z. New
- Baptist Health System, San Antonio, Texas
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- Timothy J. Pluard
- Saint Luke’s Cancer Institute, Kansas City, Missouri
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- Steven A. Toms
- Departments of Neurosurgery and Medicine, The Warren Alpert Medical School of Brown University, Providence, Rhode Island
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- Victor Tse
- Kaiser Permanente, Redwood City, California
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- Scott Peak
- Kaiser Permanente, Redwood City, California
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- John L. Villano
- University of Kentucky Markey Cancer Center, Department of Medicine, Neurosurgery, and Neurology, University of Kentucky, Lexington
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- James D. Battiste
- Oklahoma University Health Science Center, Oklahoma City
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- Paul J. Mulholland
- University College London Hospitals, London, United Kingdom
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- Michael L. Pearlman
- Blue Sky Neurology/Neuro-Oncology, Englewood, California
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- Kevin Petrecca
- Department of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill University, Montreal, Quebec, Canada
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- Michael Schulder
- Department of Neurosurgery, Zucker School of Medicine at Hofstra/Northwell, Uniondale, New York
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- Robert M. Prins
- University of California, Los Angeles
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- Alton L. Boynton
- Northwest Biotherapeutics, Inc, Bethesda, Maryland
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- Marnix L. Bosch
- Northwest Biotherapeutics, Inc, Bethesda, Maryland
書誌事項
- タイトル別名
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- A Phase 3 Prospective Externally Controlled Cohort Trial
説明
<jats:sec><jats:title>Importance</jats:title><jats:p>Glioblastoma is the most lethal primary brain cancer. Clinical outcomes for glioblastoma remain poor, and new treatments are needed.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To investigate whether adding autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L) to standard of care (SOC) extends survival among patients with glioblastoma.</jats:p></jats:sec><jats:sec><jats:title>Design, Setting, and Participants</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Interventions</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Main Outcomes and Measures</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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; <jats:italic>P</jats:italic> = .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; <jats:italic>P</jats:italic> &lt; .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; <jats:italic>P</jats:italic> = .03).</jats:p></jats:sec><jats:sec><jats:title>Conclusions and Relevance</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Trial Registration</jats:title><jats:p>ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT00045968">NCT00045968</jats:ext-link></jats:p></jats:sec>
収録刊行物
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- JAMA Oncology
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JAMA Oncology 9 (1), 112-, 2023-01-01
American Medical Association (AMA)