KYMRIAH (tisagenlecleucel) - B-cell acute lymphoblastic leukaemia (ALL) that is refractory

The Committee deems that the clinical benefit of KYMRIAH 1.2 x 106 – 6 x 108 cells (tisagenlecleucel) dispersion for infusion is substantial in the treatment of paediatric and young adult patients up to and including 25 years of age with B-cell acute lymphoblastic leukaemia (ALL) that is refractory, in relapse post-transplant or in second or later relapse.

Considering:

• the updated efficacy data from the ELIANA clinical study, confirming the results previously analysed, particularly in terms of complete remission percentage, with this remission remaining durable in some patients (approximately 1/3 to 1/2), following a median follow-up of 79.1 months between injection of KYMRIAH (tisagenlecleucel) and the database freeze for this last analysis in the ELIANA study,
• the overall survival results, with a median of 47.9 months (CI95% [19.4; NE]) in the 97 patients included (ITT population) in ELIANA, in clinical situations that are life-threatening in the short term and for which the available treatment options do not enable a complete recovery to be envisaged,
• the safety profile marked by significant short-term toxicity,
• additional experience with respect to the real-world data in the DESCAR-T registry (median follow-up duration since eligibility of 19.4 months, 19 activated centres, 99 patients treated with KYMRIAH (tisagenlecleucel)), suggesting results consistent with those of the clinical studies,
• despite the initial uncertainties identified, which persist, particularly with respect to:
  • the exact effect size compared to therapeutic management, in the absence of any robust comparison,
  • the qualitative weakness of the data in the DESCAR-T registry (data not monitored),
  • maintenance of the clinical efficacy in the long term, particularly concerning achievement of full recovery for patients in lasting remission,
  • and the absence of long-term safety data,

The Committee considers that its previous conclusions are not liable to be modified. On the basis of currently available data, KYMRIAH 1.2 x 106 – 6 x 108 cells (tisagenlecleucel) dispersion for infusion still provides a moderate clinical added value (CAV III) in the care pathway for the treatment of paediatric and young adult patients with B-cell ALL that is refractory, in relapse post-transplant or in second or later relapse.