Tisagenlecleucel (2) – Kymriah®

• Clinical trials
  • The pivotal ELIANA trial and the supportive ENSIGN trial are single-arm, multicentre Phase II trials investigating the efficacy and safety of tisagenlecleucel in children, adolescents and young adults with relapsed or refractory (r/r) B-cell acute lymphoblastic leukaemia (ALL).
  • The PEDICAR supportive study is a single-arm Phase I/II study investigating tisagenlecleucel in patients aged between 1 and 24 years with CD19-positive leukaemia or CD19-positive lymphoma who are refractory or chemoresistant.

Children, adolescents and young adults up to the age of 25 with refractory or relapsed (relapse following transplantation or second or subsequent relapse) acute lymphoblastic B-cell leukaemia (ALL)

• Consequently, the G-BA classifies the extent of the additional benefit of tisagenlecleucel alone, from a legal perspective, as unquantifiable on the basis of the criteria set out in Section 5(7) of the AM-NutzenV, taking into account the severity of the disease and the therapeutic objective in treating the disease, is non-quantifiable.
• An additional benefit exists in accordance with Section 35a(1), sentence 11, first half-sentence, of SGB V, but is non-quantifiable because the scientific evidence currently does not permit this.
• Overall assessment
  • For the assessment of the extent of the additional benefit of tisagenlecleucel for the treatment of relapsed or refractory B-cell ALL in children, adolescents and young adults, results on mortality, morbidity, quality of life and side effects are available from the pivotal single-arm Phase II ELIANA trial and the supportive single-arm Phase II ENSIGN trial.
  • The data submitted for the ELIANA and ENSIGN studies are incomplete. The current data sets lack essential information on study conduct and progression, meaning that these data sets cannot be used for the benefit assessment.
  • The data from the data cuts of 25 April 2017 for benefit assessment (ELIANA) and 1 February 2016 (ENSIGN) are subject to considerable uncertainty due to the ongoing patient recruitment and the short median follow-up period.
  • Furthermore, for these data cuts, no patient characteristics or analyses of overall survival are available for the ITT population.
  • Inherent components of treatment with tisagenlecleucel include leukapheresis, the waiting time until the product becomes available and the administration of bridging chemotherapy frequently associated with this, as well as lymphocyte-depleting chemotherapy. The impact of these components on the treatment of patients with tisagenlecleucel in a clinical care setting can only be adequately assessed by considering the ITT population.
  • Overall, due to the lack of data, no robust substantive conclusions can be drawn regarding the extent of the additional benefit.
  • On the basis of the indirect historical controls presented, and given the limited data available from the ELIANA and ENSIGN studies as well as further uncertainties regarding comparability with the studies used for the indirect comparison, no sufficiently valid conclusions regarding the extent of the additional benefit of tisagenlecleucel can currently be drawn.

Courtesy translation only, please refer to the German original.