Original Title: Arzneimittel-Richtlinie/Anlage XII: Tisagenlecleucel (Neubewertung nach Fristablauf: B-Zell-Lymphom, diffus großzelliges (DLBCL))

Authors' objectives: The Federal Joint Committee [Gemeinsamer Bundesausschuss (G-BA)] has had the legal task of carrying out an (additional) benefit assessment for all newly approved drugs with new active ingredients immediately after market entry (§ 35a SGB V). The result of this assessment is the basis for deciding how much the statutory health insurance pays for a new drug with a new active ingredient. The G-BA was commissioned to carry out the benefit assessment through the Pharmaceuticals Market Reorganisation Act [Gesetz zur Neuordnung des Arzneimittelmarktes (AMNOG)]. In the context of the early benefit assessment of medicinal products containing new active substances, the following rules apply to orphan drugs: According to the legal requirements (§ 35a SGB V), the additional medical benefit of these drugs is already considered to be proven by the approval. The G-BA determines the extent of the additional benefit for orphan drugs that do not exceed a turnover of 50 million Euros in the last twelve calendar months, on the basis of the approval and the studies justifying the approval.

Authors' results and conclusions: Tisagenlecleucel is approved for adult patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) after 2 or more lines of systemic therapy. The benefit assessment of tisagenlecleucel is based on the pivotal JULIET study (CCTL019C2201) and the subsequent long-term follow-up study. The JULIET study is a single-arm, uncontrolled, multicentre Phase II study to determine the safety and efficacy of tisagenlecleucel in adults with r/r DLBCL. Patients after 2 or more lines of chemotherapy (including rituximab and anthracycline) who were not eligible for or did not consent to stem cell therapy were included (N = 167). At the end of the JULIET study, 107 people had died, with a median survival of 8.2 months (95% CI: [5.8; 11.7]). Due to the high proportion of missing follow-up data from a significant proportion of study participants, the data on overall survival can only be considered valid up to month 60 (5 years). 5 years after study inclusion, the Kaplan-Meier estimator is 25.5 (95% CI: [18.5; 33.1]). No analyses are available with regard to patient-relevant morbidity endpoints. Due to the low response rate, no analyses are available with regard to quality of life endpoints (FACT-Lym and SF-36). With regard to safety endpoints, the study showed that AEs occur in almost all patients. The incidence of AEs, grade 3/4 AEs and SAEs is particularly high in the first 8 weeks after tisagenlecleucel infusion. The most common SAE and one of the most common grade 3 /4 AEs is cytokine release syndrome. An interpretation and comparative evaluation of the estimated survival time and safety is not possible due to the lack of a control group.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/991/#english

Year Published: 2023

URL for published report: https://www.g-ba.de/downloads/39-1464-6477/2024-02-15_AM-RL-XII_Tisagenlecleucel_D-977_EN.pdf

Requestor: The Federal Joint Committee [Gemeinsamer Bundesausschuss] (G-BA)

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/991/#nutzenbewertung

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Germany

Organisation Name: The Federal Joint Committee

Contact Address: Gutenbergstr. 13, 10587 Berlin, Germany

Contact Name: Fachberatung Medizin [Department of Medical Consultancy]

Contact Email: Fachberatung-Medizin@g-ba.de

Copyright: https://www.g-ba.de/sys/impressum/