Original Title: Arzneimittel-​​​Richtlinie/Anlage XII: Tisagenlecleucel (neubewertung nach fristablauf: diffus großzelliges B-zell-lymphom)

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 diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy Benefit assessment of tisagenlecleucel is based on the pivotal JULIET study, an uncontrolled, multicentre Phase II study to determine the safety and efficacy of tisagenlecleucel in adults with r/r DLBCL. The informative value of the results for the assessment of additional benefit is low. The data on indirect comparisons submitted by the company were deemed unsuitable for the benefit assessment due to lack of comparability with the JULIET study and were not considered. The median survival in the JULIET study was estimated at 8.2 months (95% CI: [5.8; 11.7]). At month 24, the Kaplan-Meier estimate for overall survival was 33.0 (95% CI: [25.2; 40.9]). These results may overestimate overall survival, because of the lack of long-term follow-up of patients who dropped out of the study without infusion. An interpretation and evaluation of the estimated survival time is not possible due to the missing control group. No patient-relevant morbidity endpoints were assessed. Data on quality of life were collected using the FACT-Lym and the SF-36. After the baseline evaluation data were only collected within the treated population (FAS). The analyses for the FACT-Lym and the SF-36 were not used for benefit assessment due to the missing assessment in the ITT population and the low return rates, which were already below 70% after 3 months. Adverse Events (AEs) occurred in almost all patients. Especially in the first 8 weeks after tisagenlecleucel infusion, the incidence of AE, AE of severity grade 3/4 and SAE was high. The most common SAE was the cytokine release syndrome. Furthermore, hematopoietic cytopenias occured frequently, some of which persist for longer periods. The safety of tisagenlecleucel in patients with DLBCL could not be assessed conclusively due to the lack of a control group and the partially selective collection of AEs.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/532/#english

Year Published: 2020

URL for published report: https://www.g-ba.de/downloads/39-1464-4456/2020-09-17_AM-RL-XII_Tisagenlecleucel-DLBCL_D-530_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/532/#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/