Regulatory Measures to Improve the Safety of CAR-T-Cell Treatment

Abstract

<b><i>Introduction:</i></b> Regulatory activities aim to facilitate the safe use of novel therapeutics such as genetically engineered chimeric antigen receptor (CAR)-T cells. Toxicities associated with CAR-T-cell therapies have led to modified safety management guidance in clinical trials and the implementation of post-marketing requirements. The aim of this study was to estimate the effect of individual risk-minimizing measures to evaluate the appropriateness of regulatory activities. <b><i>Methods:</i></b> We re-examined clinical trial data prior to and after the introduction of revised treatment guidelines; we analysed spontaneous adverse drug reaction (ADR) reports submitted to the EudraVigilance database in 2019/2020 regarding their completeness; and we performed a survey of treatment centres in Germany that have been qualified for the use of commercial CAR-T cells. <b><i>Results:</i></b> Lower combined incidences of severe cytokine release syndrome (CRS) as well as neurotoxicity occurred following CAR-T-cell treatment after a revision of management guidelines, suggesting earlier intervention compared to before (12.6% vs. 20.5%). Numerous post-marketing ADR reports lacked information important for case assessment. Full details on treatment indication, CRS onset, outcome, and grading were available for just 38.3% of CRS cases. Survey responses support the majority of regulatory requirements for centre qualification. Time investment was highest for training of healthcare professionals, which required an average of 6.5 staff members (range 2–20) and lasted more than 2 days per person in half of the facilities. The need to harmonize the regulatory requirements for the different CAR-T-cell therapeutics was emphasized. <b><i>Conclusion:</i></b> Defined regulatory measures can support the safe and effective use of new therapies and are indicated for structured recording of post-marketing data, and the evaluation of such measures appears to be necessary for the continuous improvement.

Sculpting nursing resilience: Transforming lives, nurturing ethics in chimeric antigen receptor T‐cell therapy

“…However, challenges remain challenging the need to be overcome to make this therapy more effective, safe, and accessible for a wider range of cancers. Recent advancement includes a computational approach where tumour cells are targeted with peptide‐centric CAR T‐cell (a new class of engineered T cells that can recognize and eradicate), 5 synthetic gene circuits, 6 traffickings and infiltration of CAR T‐cells into solid tumours by engineering them with chemokine receptors, integrins, or enzymes that can degrade the extracellular matrix 6 and for such complex treatment regimens a nurse who is well trained, knowledgeable and skilful has a crucial integral role in providing comprehensive nursing health service to patients 7–10 …”