Axicabtagen-Ciloleucel (6) – Yescarta®

• Clinical trials
  • The ZUMA-1 trial is a single-arm, multicentre Phase I/II trial investigating the efficacy and safety of axicabtagen-ciloleucel in people with relapsed or refractory DLBCL (including the subtype transformed follicular lymphoma) and primary mediastinal large B-cell lymphoma (PMBCL).
  • The Bachy 2022 study is a retrospective analysis of data from the French DESCAR-T registry. The aim is to compare the efficacy and safety of axicabtagen-ciloleucel with tisagenlecleucel in patients with DLBCL who have received at least two prior systemic therapies.

Adults with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL) following two or more systemic therapies, who are eligible for CAR-T cell therapy or stem cell transplantation

• The additional benefit is not proven.
• Additional benefit from axicabtagen-ciloleucel in adults with relapsed or refractory DLBCL and PMBCL is not proven following two or more systemic therapies compared with the appropriate comparator therapy.
• Overall assessment
  • To assess the additional benefit of axicabtagen-ciloleucel in patients with DLBCL and PMBCL following at least two lines of systemic therapy, the pharmaceutical manufacturer submitted data from the pivotal Phase I/IIZUMA-1 trial and the retrospective Bachy 2022 study. In addition, a meta-analysis of published registry data and the EUPAS32539 registry study were submitted.
  • The data presented are not suitable for benefit assessment of axicabtagen-ciloleucel.
  • The single-arm ZUMA-1 study does not allow for a comparison with the appropriate comparator therapy.
  • The Bachy 2022 study is not suitable for benefit assessment of axicabtagen-ciloleucel due to questionable equivalence in treatment arm design, a lack of systematic identification of potential confounders, and a breach of the ITT principle. Furthermore, only results relating to individual specific adverse events were presented; consequently, a comprehensive benefit-risk assessment based on the results of the Bachy 2022 study is not possible.
  • The meta-analysis presented is also unsuitable for benefit assessment, as the ITT principle was not applied and relevant information on the studies considered and the patients included is lacking. Furthermore, only results relating to specific adverse events were presented, which is why a comprehensive benefit-risk assessment based on the results of the meta-analysis provided is also not possible.
  • In the EUPAS32539 study, no comparison was made with the appropriate comparator therapy, and the ITT principle was also not applied. Furthermore, adverse events were not fully recorded, which is why a comprehensive benefit-risk assessment based on this study is not possible. Consequently, this study is also unsuitable for conducting a benefit assessment of axicabtagen-ciloleucel.
  • Consequently, additional benefit from axicabtagen-ciloleucel is not proven in adults with r/r DLBCL and PMBCL following two or more systemic therapies.

Courtesy translation only, please refer to the German original.