[Pharmaceutical Directive/Annex XII: Polatuzumab Vedotin (new therapeutic indication: diffuse large B-cell lymphoma (DLBCL), combination with rituximab, cyclophosphamide, doxorubicin and prednisone (R-CHP))]

The Federal Joint Committee [Gemeinsamer Bundesausschuss] (G-BA)
Record ID 32018004238
English, German
Original Title: Arzneimittel-Richtlinie/Anlage XII: Polatuzumab Vedotin (neues Anwendungsgebiet: Diffus großzelliges B-Zell-Lymphom, Kombination mit Rituximab, Cyclophosphamid, Doxorubicin und Prednison (R-CHP))
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: Polatuzumab Vedotin (Polivy®) in combination with rituximab, cyclophosphamide, doxorubicin and prednisone (Pola + R-CHP) is indicated for the treatment of adult patients with previously untreated diffuse large B-cell lymphoma (DLBCL). The benefit assessment of the new therapeutic indication is based on the multicentre, double-blind, randomized POLARIX study comparing Pola + R-CHP (N = 440) versus rituximab in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP; N = 439) of the first data cut-off from 28 June 2021, which represents the primary analysis of progression-free survival. As part of the written statement procedure, the pharmaceutical company submitted the results of the third data cut-off from 15 June 2022, including the final analysis of overall survival. This data cut-off is the basis of the amendment of the benefit assessment. With regard to the endpoint of overall survival, there was no statistically significant difference between Pola + R-CHP and R-CHOP. In the endpoint category of morbidity, the endpoint of event-free survival (EFS) showed a minimal statistically significant difference in favour of Pola + R-CHP (Hazard ratio [95% confidence interval]; p-value: 0,785 [0,617; 0,999]; 0,048). This effect is not considered sufficiently reliable, because of the low magnitude of the effect and uncertainties in the operationalisation of EFS. For the patient-reported endpoints on morbidity and quality of life, no statistically significant differences were observed with the exception of chemotherapy-induced neurotoxicity, assessed by the FACT/GOG-NTX. There was a statistically significant advantage of Pola + R-CHP over R-CHOP at the end of treatment. However, the clinical relevance of this effect remains unclear, because of lack of standardised irrelevance thresholds (Hedges` g). For the endpoint category side effects, no statistically significant difference was observed between the treatment arms for serious and severe adverse events (AE) or in therapy discontinuations due to AE. Based on the study design, the study's potential for bias is considered low.
Project Status: Completed
Year Published: 2022
Requestor: The Federal Joint Committee [Gemeinsamer Bundesausschuss] (G-BA)
English language abstract: An English language summary is available
Publication Type: Full HTA
Country: Germany
MeSH Terms
  • Lymphoma, Large B-Cell, Diffuse
  • Antibodies, Monoclonal
  • Immunoconjugates
  • Antineoplastic Combined Chemotherapy Protocols
  • Rituximab
  • Cyclophosphamide
  • Doxorubicin
  • Prednisone
  • diffuse large B-cell lymphoma
  • adult
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/
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