Identification of the risks in CAR T-cell therapy clinical trials in China: a Delphi study

Abstract

Aims: Within the past few years, there has been tremendous growth in clinical trials of chimeric antigen receptor (CAR) T-cell therapies. Unlike those of many small-molecule pharmaceuticals, CAR T-cell therapy clinical trials are fraught with risks due to the use of live cell products. The aim of this study is to reach a consensus with experts on the most relevant set of risks that practically occur in CAR T-cell therapy clinical trials. Methods: A Delphi method of consensus development was used to identify the risks in CAR T-cell therapy clinical trials, comprising three survey rounds. The expert panel consisted of principal investigators, clinical research physicians, members of institutional ethics committees, and Good Clinical Practice managers. Results: Of the 24 experts invited to participate in this Delphi study, 20 participants completed Round 1, Round 2, and Round 3. Finally, consensus (defined as >80% agreement) was achieved for 54 risks relating to CAR T-cell clinical trials. Effective interventions related to these risks are needed to ensure the proper protection of subject health and safety. Conclusion: The Delphi method was successful in gaining a consensus on risks relevant to CAR T-cell clinical trials in a geographically diverse expert association. It is hoped that this work can benefit future risk-based quality management in clinical trials and can potentially promote the better development of CAR T-cell therapy products.

Lisocabtagene Maraleucel (Breyanzi)

“…50 There is particular uncertainty in terms of the long-term harms and benefits of these therapies, where current clinical trial data do not provide clinical insights on long-term outcomes. [61][62][63] Patients who receive CAR T-cell therapies may also experience psychosocial burdens and may require community supports. 45,50 Authors have noted that CAR T-cell therapies may be considered a treatment of "last resort," 62 and that many patients who feel they lack alternative therapeutic options may be willing to undergo CAR T-cell treatments that bear risks of harm.…”