(CSPOT45) Post-marketing Safety Assessment of CAR T-cell Therapies: Analysis of Individual Case Safety Reports in the VigiBase

Background: Chimeric Antigen Receptor (CAR)-T cell therapies have emerged as potential therapy for hematological malignancies, however, their safety profiles should be monitoring after approval. Therefore, the Saudi Food and Drug Authority (SFDA) has established a Proactive Drug Safety Monitoring Program to monitor the safety of CAR T-cell therapies that registered in Saudi Arabia.

Objectives: To describe and analyze Individual Case Safety Reports (ICSRs) associated with the use of SFDA approved CAR-T cell therapies reported to the World Health Organization (WHO) database “VigiBase” in order to identify potential signals.

Methods: A retrospective pharmacovigilance study was conducted to assess adverse drug reaction (ADRs) that were associated with use of approved CAR-T cell therapies in Saudi Arabia (Tisagenlecleucel, Axicabtagene ciloleucel, and Ciltacabtagene autoleucel ). All ICSRs reported to VigiBase from inception to March 31st were extracted and ADRs were classified according to MedDRA System Organ Class (SOC) and Preferred Term (PT). A descriptive analysis of the main characteristics of the ADRs reports was conducted by each product. A crosschecking of the accredited authorities and local labels was preformed to exclude labeled ADRs. Lastly, a systematic search of literature, local and global spontaneous reports, and Periodic Benefit-Risk Evaluation Reports was conducted on unlabeled ADRs to identify potential signals.

Results: A total of 9,783 ADEs were identified within VigiBase, (Tisagenlecleucel (n= 3364), Ciltacabtagene autoleucel (n= 751), and Axicabtagene ciloleucel (n= 5668)). The United States was the most reported country for all products. The majority of ADEs were serious. Of these, 9,734 ADRs were excluded due to the following; labeled in the local Summary of Product Characteristics (SPC), disease related, vague events, duplicates or missing important information. The labelness assessment resulted in requesting local labelling update of 12 ADEs (Tisagenlecleucel (n=2), Ciltacabtagene autoleucel (n=3), and Axicabtagene ciloleucel (n=7)). The remaining 37 ADEs were considered as safety signals and were referred for comprehensive safety evaluation.

Conclusions: Based on the analysis performed, the retrieved data from ADE reports reveals new potential safety signals with the use of CAR T-cell therapies. However, it highlights considerable variability in the quality and completeness of ADE reports. Therefore, regulatory bodies should raise awareness and develop procedures in order to improve quality of ADE reports.