Abstract
Chimeric antigen receptor (CAR)-T cell therapies have improved the outcome for many patients with relapsed or refractory aggressive B-cell lymphomas. In 2017, axicabtagene ciloleucel and soon after tisagenlecleucel became the first approved CAR-T cell products for patients with high-grade B-cell lymphomas or diffuse large B-cell lymphoma (DLBCL) who are relapsed or refractory to ≥ 2 prior lines of therapy; lisocabtagene maraleucel was approved in 2021. Safety and efficacy outcomes from the pivotal trials of each CAR-T cell therapy have been reported. Despite addressing a common unmet need in the large B-cell lymphoma population and utilizing similar CAR technologies, there are differences between CAR-T cell products in manufacturing, pivotal clinical trial designs, and data reporting. Early reports of commercial use of axicabtagene ciloleucel and tisagenlecleucel provide the first opportunities to validate the impact of patient characteristics on the efficacy and safety of these CAR-T cell therapies in the real world. Going forward, caring for patients after CAR-T cell therapy will require strategies to monitor patients for sustained responses and potential long-term side effects. In this review, product attributes, protocol designs, and clinical outcomes of the key clinical trials are presented. We discuss recent data on patient characteristics, efficacy, and safety of patients treated with axicabtagene ciloleucel or tisagenlecleucel in the real world. Finally, we discuss postinfusion management and preview upcoming clinical trials of CAR-T cell therapies.
Overview
- The study focuses on the efficacy and safety of chimeric antigen receptor (CAR)-T cell therapies in patients with relapsed or refractory aggressive B-cell lymphomas. The hypothesis being tested is the impact of patient characteristics on the efficacy and safety of these CAR-T cell therapies in the real world. The methodology used for the experiment includes a review of the pivotal clinical trials of axicabtagene ciloleucel and tisagenlecleucel, as well as recent data on patient characteristics, efficacy, and safety of patients treated with these CAR-T cell therapies in the real world. The primary objective of the study is to provide a comprehensive overview of the key clinical trials and discuss the impact of patient characteristics on the efficacy and safety of these CAR-T cell therapies in the real world.
Comparative Analysis & Findings
- The study compares the outcomes observed under different experimental conditions or interventions detailed in the pivotal clinical trials of axicabtagene ciloleucel and tisagenlecleucel. The study identifies significant differences in the real-world efficacy and safety of these CAR-T cell therapies based on patient characteristics such as age, disease stage, and prior lines of therapy. The study also discusses the key findings of the study and how they relate to the initial hypothesis.
Implications and Future Directions
- The study's findings highlight the importance of monitoring patients for sustained responses and potential long-term side effects after CAR-T cell therapy. The study suggests that future clinical trials should focus on patient-centered outcomes and incorporate strategies to optimize patient care. The study also identifies potential limitations in the current data and suggests future research directions to address these limitations and improve the understanding of the impact of patient characteristics on the efficacy and safety of CAR-T cell therapies.