Lenalidomide with Rituximab for Previously Treated Follicular Lymphoma and Marginal Zone Lymphoma: An Evidence Review...

The National Institute for Health and Care Excellence (NICE) invited the manufacturer (Celgene) of lenalidomide (Revlimid^®), as part of the Single Technology Appraisal (STA) process, to submit evidence for the clinical effectiveness and cost-effectiveness of lenalidomide in combination with rituximab (MabThera^®), together referred to as R², for the treatment of adults with treated follicular lymphoma (FL) or marginal zone lymphoma (MZL). Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Centre+, was commissioned to act as the independent Evidence Review Group (ERG). This paper summarises the company submission (CS), presents the ERG's critical review on the clinical and cost-effectiveness evidence in the CS, highlights the key methodological considerations, and describes the development of the NICE guidance by the Appraisal Committee. The CS included one relevant study, for the comparison of R² versus rituximab monotherapy (R-mono): the AUGMENT trial. In addition, the company performed an unanchored indirect comparison of R² versus rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) and rituximab combined with cyclophosphamide, vincristine, and prednisolone (R-CVP), using data for R² from the AUGMENT trial and pooled data for R-CHOP/R-CVP from the Haematological Malignancy Research Network (HMRN) database. During the STA process, the company provided an addendum containing evidence on only the FL population, in line with the marketing authorisation obtained at that time, which did not include MZL. The probabilistic incremental cost-effectiveness ratios (ICERs) presented by the company were £27,768 per quality-adjusted life year (QALY) gained for R² versus R-CHOP, £41,602 per QALY gained for R² versus R-CVP, and £23,412 per QALY gained for R² versus R-mono. The ERG's concerns included the validity of the unanchored comparison, the unavailability of a state transition model to verify the outcomes of the partitioned survival model, substantial uncertainty in survival curves, and potential over-estimation of utility values. The revised ERG base case resulted in ICERs ranging from £16,874 to £44,888 per QALY gained for R² versus R-CHOP, from £23,135 to £59,810 per QALY gained for R² versus R-CVP, and from £18,779 to £27,156 per QALY gained for R² versus R-mono. Substantial uncertainty remained around these ranges. NICE recommended R² within its marketing authorisation, as an option for previously treated FL (grade 1-3A) in adults, contingent on the company providing lenalidomide according to the commercial arrangement.