Opportunities and challenges associated with the evaluation of chimeric antigen receptor T cells in real-life

McGrath, Eoin; Chabannon, Christian; Terwel, Sofie R.; Bonini, Chiara; Kuball, Jürgen

doi:10.1097/cco.0000000000000665

Cited by 15 publications

(14 citation statements)

References 12 publications

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“…To prevent inconsistency in the capturing of the elements, clear definitions need to be formulated [13]. In this context, the defined core data sets by the European Society for Blood and Marrow Transplantation Registry and the European Cystic Fibrosis Society Patient Registry can be used, which have been shown to support regulatory decision making [16][17][18][19].…”

Section: Discussionmentioning

confidence: 99%

Capturing Data in Rare Disease Registries to Support Regulatory Decision Making: A Survey Study Among Industry and Other Stakeholders

Jonker

Vries

Berg³

et al. 2021

Drug Saf

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Introduction In rare diseases, registry-based studies can be used to provide natural history data pre-approval and complement drug efficacy and/or safety knowledge post-approval. Objective The objective of this study was to investigate the opinion of stakeholders about key aspects of rare disease registries that are used to support regulatory decision making and to compare the responses of employees from industry to other stakeholders. Methods A web-based survey was used to gauge the importance of (1) common data elements (including safety outcomes), (2) data quality and (3) governance aspects that are generic across different rare diseases. The survey included 47 questions. The data were collected in the period April-October 2019. Results Seventy-three respondents completed ≥ 80% of the survey. Most of the respondents were from the industry (n = 42, 57%). For safety data, 31 (42%) respondents were in favour of collecting all adverse events. For data quality, the respondents found a level of 30% reasonable for source data verification. For missing data, a level of 20% was considered acceptable. Compared to responders from industry, the other stakeholders found it less relevant to share data with industry and found it less acceptable if the registry is financed by industry. Conclusions This study showed that the opinion towards data and governance is well aligned across parties, and issues of data and governance on their own should not pose a barrier to collaboration. This finding is supportive of the European Medicines Agency's efforts to encourage stakeholders to work with existing registries when collecting data to support regulatory decision making.

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Section: Discussionmentioning

confidence: 99%

Capturing Data in Rare Disease Registries to Support Regulatory Decision Making: A Survey Study Among Industry and Other Stakeholders

Jonker

Vries

Berg³

et al. 2021

Drug Saf

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“…Existing infrastructure such as the one used by EBMT could retrieve data on all HSPC-GT procedures and allow comparison with HSCT. This approach has been used to capture information on long-term follow-up of patients treated with CAR-T cells, but its success and broader applicability are still under evaluation 32 .…”

Section: Discussionmentioning

confidence: 99%

Gene therapy with hematopoietic stem and progenitor cell for monogenic disorders: a systematic review and meta-analysis

Tucci

Galimberti

Naldini³

et al. 2021

Preprint

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To provide an assessment of the safety of ex-vivo gene therapy (GT) with hematopoietic stem and progenitor cells (HSPC), we reviewed in a systematic manner the literature on monogenic diseases to describe survival, genotoxicity and engraftment of gene corrected HSPC, across vector platforms and diseases. From 1995 to 2020, 55 trials for 14 diseases met inclusion criteria and 406 patients with primary immunodeficiencies (55.2%), metabolic diseases (17.0%), haemoglobinopathies (24.4%) and bone marrow failures (3.4%) were treated with gammaretroviral vector (γRV) (29.1%), self-inactivating γRV (2.2%) or lentiviral vectors (LV) (68.7%). The pooled overall incidence rate of death was 0.9 per 100 person-years of observation (PYO) (95%CI = 0.37–2.17). There were 21 genotoxic events out of 1504.02 PYO. All these events occurred in γRV trials (0.99 events per 100 PYO, 95%CI = 0.18–5.43) for primary immunodeficiencies. Pooled rate of engraftment was 86.1% (95%CI = 66.9–95.0%) for γRV and 99.0% (95%CI = 95.1–99.8%) for LV HSPC-GT (p = 0.002). A comprehensive meta-analysis on HSPC-GT showed stable reconstitution of haematopoiesis in most recipients with superior engraftment and safer profile in patients receiving LV-transduced HSPC.

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“… 61 The EBMT registry covering transplantations and cellular immune therapies like CAR T cells will be well-suited to serve as a potential backbone for these studies, but would need to be extended. 62 , 63 These studies should also include inquiries into the socio-economic impacts and quality of life for patients in order to cover all aspects of earlier financial investments and future societal gains. 62 …”

Section: Ex Vivo T Cell Engineering Strategies Focusing On Defined Subsetsmentioning

confidence: 99%

“… 62 , 63 These studies should also include inquiries into the socio-economic impacts and quality of life for patients in order to cover all aspects of earlier financial investments and future societal gains. 62 …”

Section: Ex Vivo T Cell Engineering Strategies Focusing On Defined Subsetsmentioning

confidence: 99%

Allogeneic Stem Cell Transplantation Platforms With Ex Vivo and In Vivo Immune Manipulations: Count and Adjust

et al. 2021

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Various allogeneic (allo) stem cell transplantation platforms have been developed over the last 2 decades. In this review we focus on the impact of in vivo and ex vivo graft manipulation on immune reconstitution and clinical outcome. Strategies include anti-thymocyte globulin-and post-transplantation cyclophosphamide-based regimens, as well as graft engineering, such as CD34 selection and CD19/αβT cell depletion. Differences in duration of immune suppression, reconstituting immune repertoires, and associated graft-versus-leukemia effects and toxicities mediated through viral reactivations are highlighted. In addition, we discuss the impact of different reconstituting repertoires on donor lymphocyte infusions and post allo pharmacological interventions to enhance tumor control. We advocate for precisely counting all graft ingredients and therapeutic drug monitoring during conditioning in the peripheral blood, and for adjusting dosing accordingly on an individual basis. In addition, we propose novel trial designs to better assess the impact of variations in transplantation platforms in order to better learn from our diversity of "counts" and potential "adjustments." This will, in the future, allow daily clinical practice, strategic choices, and future trial designs to be based on data guided decisions, rather than relying on dogma and habits.

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Opportunities and challenges associated with the evaluation of chimeric antigen receptor T cells in real-life

Cited by 15 publications

References 12 publications

Capturing Data in Rare Disease Registries to Support Regulatory Decision Making: A Survey Study Among Industry and Other Stakeholders

Capturing Data in Rare Disease Registries to Support Regulatory Decision Making: A Survey Study Among Industry and Other Stakeholders

Gene therapy with hematopoietic stem and progenitor cell for monogenic disorders: a systematic review and meta-analysis

Allogeneic Stem Cell Transplantation Platforms With Ex Vivo and In Vivo Immune Manipulations: Count and Adjust

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