YESCARTA (axicabtagene ciloleucel) - Large B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMLBCL)

The Committee deems that the clinical benefit of YESCARTA 0.4 - 2 x 10 8 cells (axicabtagene ciloleucel) dispersion for infusion remains substantial in “the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL), after two or more lines of systemic therapy” and at the MA dosages.

Considering:

• the updated data from the ZUMA-1 study, following a median follow-up of 63.1 months, which confirms the previously analysed results, particularly in terms of complete response (58% of patients in the mITT population, of whom 30% still in complete response at the time of the analysis after 60 months), and overall survival (median overall survival of 25.8 months in the mITT population; 5-year survival probability estimated to be 42.6%), in life-threatening clinical situations in which the treatment options are limited and do not enable remission to be envisaged,
• the role of YESCARTA (axicabtagene ciloleucel) compared to KYMRIAH (tisagenlecleucel), which remains difficult to determine given the major methodological limitations of the indirect comparison provided,
• the safety profile marked by significant short-term toxicity,
• additional experience with respect to the real-world data for YESCARTA (axicabtagene
  ciloleucel) in the French DESCAR-T registry (27 activated centres, 756 treated patients, median follow-up of 15 months since eligibility), which are consistent with the clinical data (ZUMA-1),
• and the initial uncertainties identified, which persist despite the Transparency Committee’s requests, particularly with respect to:
  • the exact effect size compared to historic management, in the absence of any robust comparison,
  • 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, the Committee deems that YESCARTA 0.4 - 2 x 108 cells (axicabtagene ciloleucel) dispersion for infusion provides a moderate clinical added value (CAV III) in terms of efficacy compared to the historic management of relapsed or refractory diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma after two or more lines of systemic therapy, based on various chemotherapies.