Axicabtagen-Ciloleucel (5) – Yescarta®

• Clinical trials
  • In the ongoing, open-label Phase III ZUMA-7 trial, axicabtagen-ciloleucel is being compared with induction therapy using R-ICE, R-DHAP, R-ESHAP and R-GDP, followed by high-dose chemotherapy (HDCT) with autologous stem cell transplantation (SCT).
  • For the benefit assessment, the pharmaceutical manufacturer is presenting data from the single-arm ALYCANTE trial, in which 62 patients with relapsed or refractory DLBCL, for whom autologous stem cell transplantation is not an option, were treated with axicabtagen-ciloleucel following first-line therapy.

a) Adults with diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL), who are eligible for high-dose therapy and who relapse or are refractory to first-line therapy within 12 months of its completion

• In the overall assessment, a non-quantifiable additional benefit is identified for axicabtagen-ciloleucel compared with induction chemotherapy with R-GDP, R-ICE or R-DHAP followed by high-dose therapy with autologous stem cell transplantation.
• Taking into account the available limitations as a whole, the certainty of the evidence for the identified additional benefit is classified as ‘hint’.
• mortality
  • For the endpoint of overall survival, a statistically significant difference in favour of axicabtagen-ciloleucel is observed. The extent of the prolongation in survival is assessed as a minor improvement.
• Morbidity – Failure of the curative treatment approach
  • In the morbidity endpoint category, based on the results for the event-free survival (EFS) endpoint, an advantage for axicabtagen-ciloleucel is observed with regard to the failure of the curative treatment approach. However, the extent of this advantage cannot be quantified due to significant uncertainties.
  • In the ZUMA-7 trial, EFS was defined as the time from randomisation to the first occurrence of any of the following events: death from any cause, disease progression, stable disease (SD) as the best response up to study day 150 after randomisation, or the start of a new lymphoma treatment.
  • Overall, therefore, despite existing uncertainties and against the backdrop of large effects, the results on EFS are considered sufficiently meaningful in almost all available analyses to allow an assessment of whether the curative treatment approach has failed.
• Morbidity – Symptoms (EORTC QLQ-C30) and Health Status (EQ-5D VAS)
  • No suitable data are available on symptoms (assessed using the EORTC-QLQ-C30) and health status (assessed using the EQ-5D-VAS) due to an excessively high proportion of missing values and the high proportion of patients missing from the analysis.
• Health-related quality of life
  • The results on health-related quality of life are not used for the benefit assessment.
• Side effects
  • The available analyses for the endpoints relating to side effects are not suitable for the benefit assessment. Consequently, it is not possible to weigh up the benefits and harms of axicabtagen-ciloleucel on the basis of the data presented.
• Overall assessment / Conclusion
  • For the benefit assessment of axicabtagen-ciloleucel, data are available from the open-label, randomised Phase III ZUMA-7 trial on mortality, morbidity, quality of life and side effects compared with induction therapy with R-GDP, R-ICE or R-DHAP followed by high-dose therapy with autologous stem cell transplantation.
  • With regard to overall survival, there is a statistically significant difference in favour of axicabtagen-ciloleucel. The extent of the prolongation in survival time is assessed as a minor improvement.
  • In the morbidity endpoint category, based on the results for the event-free survival (EFS) endpoint regarding the failure of the curative treatment approach, an advantage for axicabtagen-ciloleucel is observed. However, the extent of this advantage cannot be quantified due to significant uncertainties.
  • No suitable data are available on symptoms (assessed using the EORTC-QLQ-C30) or health status (assessed using the EQ-5D-VAS). This also applies to the data on health-related quality of life (assessed using the EORTC-QLQ-C30).
  • The available analyses for the endpoints relating to side effects are not suitable for a benefit assessment. Consequently, it is not possible to weigh up the benefits and harms of axicabtagen-ciloleucel on the basis of the data presented.

b) Adults with diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) who are not eligible for high-dose therapy and who relapse or are refractory to first-line therapy within 12 months of its completion

• An additional benefit of axicabtagen-ciloleucel over the appropriate comparator therapy is not proven.
• As this is not a comparison with the appropriate comparator therapy, the ALYCANTE study is not suitable for benefit assessment.
• Overall, therefore, there are no suitable data available for assessing the additional benefit of axicabtagen-ciloleucel compared with the appropriate comparator therapy. Consequently, the additional benefit is not proven.

Courtesy translation only, please refer to the German original.