Summary of US Food and Drug Administration Chimeric Antigen Receptor (CAR) T-Cell Biologics License Application Approvals From a Statistical Perspective

The approval of tisagenlecleucel and axicabtagene ciloleucel in 2017 marked a milestone in the development of oncology therapies. Since 2017, the breakthrough in treatment or even cure of previously intractable diseases represented by this new class of cancer treatments has continued with subsequent chimeric antigen receptor T (CAR T)-cell approvals. To date, the US Food and Drug Administration has approved five autologous CAR T-cell products for seven indications. A feature of autologous CAR T-cell products that differentiates them from traditional oncology drugs is that they need to be manufactured specifically for each patient. This feature has implications in study design, statistical analyses, and interpretation of study results. In this article, we share our experiences in the statistical review of CAR T-cell products and provide considerations for the design and statistical analyses of CAR T-cell trials. We also describe how the newly adopted estimand framework for clinical trials can help clarify nuanced issues in CAR T-cell trial design.

Automated summary

The approval of autologous CAR T-cell therapies in 2017 has been an important milestone in the field of oncology. These therapies have shown breakthroughs in treating previously incurable diseases, and their unique manufacturing process for each patient presents challenges in study design and statistical analyses. This article shares experiences in statistical review and provides considerations for CAR T-cell trial design. The adoption of the estimand framework in clinical trials is also discussed for addressing nuanced issues in CAR T-cell trials.