Original Title: Arzneimittel-Richtlinie/Anlage XII: Ciltacabtagen autoleucel (rezidiviertes / refraktäres Multiples Myelom, nach mind. 3 Vortherapien)

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: Ciltacabtagene autoleucel, a novel BCMA directed chimeric antigen receptor (CAR) T-cell therapy is approved for the treatment of multiple myeloma in adults who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti CD38 antibody and whose disease has worsened since the last treatment. The benefit assessment is based on the pivotal CARTITUDE-1 study, an one-arm, open-label and multicentric phase-Ib/II-study. The primary objective for the phase-II-cohort was to measure the objective response rate using IMWG criteria (partial response or better). The bias potential is considered high due to the missing controll group. An indirect treatment comparison was rejected because of methodological shortcomings and limited comparability of study populations (missing positivity) between clinical and control group (LocoMMotion). Therefore it is not possible to draw conclusions on mortality and morbidity endpoints due to the missing controll group. Of 124 patients in the ITT-Population, 39 (31,5%) deceased at the time of the relevant data cut off date from 21.02.2022. Median overall survival was not reached yet (95%-KI: [31,47; n.o.]) and the median observation time was 28.55 months. Side effects were mainly collected between the day of infusion and day 100 after infusion. Nearly every AE of special interest occurred in the trial, especially the cytokine release syndrom (CRS). Furthermore the CRS was the most observed SAE. The safety assessment is limited due to differences in reporting between treatment phases and the missing control group. In summary, the curative potential of the CAR-T in this patient population can not be fully assessed due to the missing controll group.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/924/#english

Year Published: 2023

URL for published report: https://www.g-ba.de/downloads/39-1464-6126/2023-08-17_AM-RL-XII_Ciltacabtagen-autoleucel_D-919_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/924/#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/