Monitoring CAR-T-Cell Therapies Using the Nordic Healthcare Databases
- 50 Downloads
Following intense research efforts, modulation of the immune system has finally proved to be a viable approach for treating malignant disease. Recently, chimeric antigen receptor redirected T cells have achieved promising outcomes in patients with B-cell malignancies and they are currently also being investigated in other haematological malignancies, solid tumours and viral infections. Compared with traditional biopharmaceuticals, the properties of genetically modified chimeric antigen receptor redirected T-cell therapies differ in many aspects, thereby posing challenges in terms of post-authorisation data collection and data analysis. We believe that the network of population-based Nordic healthcare databases has some characteristics that can help provide important data on these new types of advanced products. In particular, the possibility of very long follow-up periods with a limited loss to follow-up is an important strength. Given the limited source population and slow access to data, a Nordic chimeric antigen receptor redirected T-cell monitoring project should be seen as complementary to other surveillance initiatives.
Compliance with Ethical Standards
Morten Andersen and Torbjörn Callréus belong to the Pharmacovigilance Research Group at the Department of Drug Design and Pharmacology, University of Copenhagen, receiving funding by the Novo Nordisk Foundation (NNF15SA0018404). No funding was specifically received for the preparation of this article.
Conflict of Interest
Mats Jerkeman has received research grants from Gilead, Abbvie, Janssen and Celgene, and personal fees from Gilead, Janssen, Acerta, Roche and Celgene. Tarec Christoffer El-Galaly has received travel grants from Takeda (ICML 2017) and Roche (ASH 2016) and has been employed by F. Hoffmann-La Roche, Ltd. since January 2019. Morten Andersen has participated in research projects funded by AstraZeneca, H. Lundbeck & Mertz, Novartis, Pfizer and Janssen, with grants paid to the institutions where he has been employed, and has personally received fees from Medicademy, the Danish Pharmaceutical Industry Association, for leading and teaching pharmacoepidemiology courses. Torbjörn Callréus and Peter de Nully Brown have no conflicts of interest that are directly relevant to the content of this article.
- 8.Commission implementing decision granting marketing authorisation under Regulation (EC) No. 726/2004 of the European Parliament and of the Council for “Yescarta—axicabtagene ciloleucel”, an orphan medicinal product for human use. http://ec.europa.eu/transparency/regdoc/rep/3/2018/EN/C-2018-5718-F1-EN-MAIN-PART-1.PDF. Accessed 1 Nov 2018.
- 9.Commission implementing decision granting marketing authorisation under Regulation (EC) No. 726/2004 of the European Parliament and of the Council for “Kymriah—tisagenlecleucel”, an orphan medicinal product for human use. http://ec.europa.eu/transparency/regdoc/rep/3/2018/EN/C-2018-5717-F1-EN-MAIN-PART-1.PDF. Accessed 1 Nov 2018.
- 12.Shi Q, Schmitz N, Ou FS, Dixon JG, Cunningham D, Pfreundschuh M, et al. Progression-free survival as a surrogate end point for overall survival in first-line diffuse large B-cell lymphoma: an individual patient-level analysis of multiple randomized trials (SEAL). J Clin Oncol. 2018;36(25):2593–602.CrossRefGoogle Scholar
- 14.Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, et al. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014;32(31):3490–6.CrossRefGoogle Scholar
- 20.Summary of risk management plan for YESCARTA (axicabtagene ciloleucel). https://www.ema.europa.eu/documents/rmp-summary/yescarta-epar-risk-management-plan-summary_en.pdf. Accessed 1 Nov 2018.
- 21.Summary of the risk management plan for Kymriah (tisagenlecleucel). https://www.ema.europa.eu/documents/rmp-summary/kymriah-epar-risk-management-plan-summary_en.pdf. Accessed 1 Nov 2018.
- 25.Li L, Kulldorff M. A conditional maximized sequential probability ratio test for pharmacovigilance. Stat Med. 2010;29(2):284–95.Google Scholar
- 28.Lim J, Walley R, Yuan J, Liu J, Dabral A, Best N, et al. Minimizing patient burden through the use of historical subject-level data in innovative confirmatory clinical trials: review of methods and opportunities. Ther Innov Regul Sci. 2018;52(5):546–59.Google Scholar
- 39.Chatzidionysiou K, Hetland ML, Frisell T, Di GD, Hellgren K, Glintborg B, et al. Opportunities and challenges for real-world studies on chronic inflammatory joint diseases through data enrichment and collaboration between national registers: the Nordic example. RMD Open. 2018;4(1):e000655.CrossRefGoogle Scholar