Safety and efficacy of autologous tumour cell vaccines as a cancer therapeutic to treat solid tumours and haematological malignancies: a meta-analysis protocol for two systematic reviews

Abstract

IntroductionAutologous cancer cell vaccines are promising personalised immunotherapeutic options for solid and haematological malignancies that uses the patient’s own cells to arm an immune response. Evidence suggests that among patients receiving these vaccines, those who mount an immune response against their own tumour cells have better prognosis, and a myriad of preclinical studies have demonstrated the same. Recently, two autologous cell vaccines Vigil and OncoVAX have made it to phase III clinical trials. Here, we outline a protocol to be used for two separate systematic reviews using a parallel approach for inclusion criteria, data extraction and analysis for autologous cell vaccines in (1) solid and (2) haematological malignancies. We aim to review evidence from controlled and uncontrolled interventional studies of autologous cell vaccines administered to patients with cancer to determine their historical efficacy (with or without associated adjuvants or modifications) with clinical response rates and safety outcomes being of particular importance.Methods and analysisWe will search MEDLINE (OVID interface, including In-Process and Epub Ahead of Print), Embase (OVID interface) and the Cochrane Central Register of Controlled Trials (Wiley interface) for articles published from 1947 until 30 July 2018 (date search was performed). Studies will be screened first by title and abstract, then by full-text in duplicate. Interventional trials that report the use of an autologous cell vaccine to patients with cancer of any age will be included. The primary outcomes of interest in this review are clinical response (complete or overall/objective response) and safety outcomes (adverse events). Secondary outcomes include immune response, disease-free survival and overall survival. The risk of bias within studies will be assessed using the appropriate Cochrane Risk of Bias tool. If appropriate, a random effects meta-analysis will be performed to synthesise the data and report summary estimates of effect. Statistical heterogeneity will be assessed using the I2 statistic.Ethics and disseminationEthics approval is not required for this systematic review protocol as the review will solely use published literature. Results will be submitted to peer-reviewed journals for publication and presented to relevant stakeholders and scientific meetings.PROSPERO registration numberCRD42019140187.

Safety and efficacy of autologous whole cell vaccines in hematologic malignancies: A systematic review and meta‐analysis

“…Analysis of other secondary outcomes, including patient experience, health‐related quality of life, and health utility measures as detailed in the protocol could not be conducted due to the limited number of studies and lack of outcome reporting 17 …”

“…The protocol for this systematic review was prospectively registered on PROSPERO (CRD42019140187) and has been previously published. 17 This report follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. A completed PRISMA checklist can be found in Appendix 1.…”

Identifying effect modifiers of CAR-T cell therapeutic efficacy: a systematic review and individual patient data meta-analysis protocol

“…We will use a modified version of the Institute of Health Economics tool to assess risk of bias [ 28 , 29 ]. This modified tool was successfully implemented in previous reviews consisting of predominately single arm studies [ 12 , 30 ]. As we have previously described, the tool evaluates the following elements: study objective, design, study population, intervention and cointerventions, outcome measures, statistical analysis, results, and conclusions, as well as conflicts of interest.…”

The current clinical landscape of personalized cancer vaccines

“…Autologous tumor cell vaccines can be rendered more immunogenic by admix with immunomodulatory adjuvants. In a phase III/b clinical trial with stage II and II colon cancer patients, OncoVax (irradiated autologous colon tumor cells admixed with Bacillus Calmette-Guérin [BCG]) significantly improved the overall survival (OS) and PFS in patients with stage-II cancer (p = 0⋅011) [19,20]. Furthermore, over a median follow-up period of 5.3 years, a 44% risk reduction for recurrence was observed in all the patients treated with OncoVAX (p = 0.023) [19,20].…”

“…In a phase III/b clinical trial with stage II and II colon cancer patients, OncoVax (irradiated autologous colon tumor cells admixed with Bacillus Calmette-Guérin [BCG]) significantly improved the overall survival (OS) and PFS in patients with stage-II cancer (p = 0⋅011) [19,20]. Furthermore, over a median follow-up period of 5.3 years, a 44% risk reduction for recurrence was observed in all the patients treated with OncoVAX (p = 0.023) [19,20]. Other autologous tumor cell vaccines that were prepared with BCG as an adjuvant also demonstrated the ability to improve overall survival in advanced metastatic prostate cancer and stage-III/IV melanoma [9,21].…”