Systematic Literature Review of the Cost-Effectiveness of Treatments, Costs/Resource Use, and Quality of Life in Patients with Mantle Cell Lymphoma

Abstract Introduction Mantle cell lymphoma (MCL) is a rare but often aggressive subtype of non-Hodgkin's lymphoma, with many patients experiencing short survival. While both first and subsequent-line therapies are available, it is unclear what health economic evidence is available for treatments. To provide context for economic evaluations, it is also important to understand the economic burden of MCL and the quality of life which patients experience. Our study aims to comprehensively understand health economic (costs and resource-use, and economic evaluations) and health-related quality of life (HRQoL) evidence base for patients with MCL through three systematic literature reviews (SLRs). Methods Search strategies were designed to capture studies reporting economic or HRQoL outcomes for patients with MCL. Searches were date-limited in order to identify studies published in the last 10 years (2007-current). The following electronic databases were searched: MEDLINE, Embase, NHS Economic Evaluation Database (NHS EED), and EconLit. In addition, we searched congress abstracts (at ASCO, ASH, ISPOR, AMCP, EHA, and ESMO proceedings) presented over the previous 2 years. Potential publications were screened in duplicate by 2 reviewers. Additional online searches were carried out to identify health technology assessment (HTA) submission documents reporting health economic evaluations for patients treated with pharmacological interventions. All searches were conducted in October 2017, and were updated in March 2018. Results The SLR identified 11 economic evaluations reported across 16 publications, and 7 studies reporting data for costs or resource-use. Table 1 presents a summary of the economic evaluations that reported incremental cost effectiveness ratios (ICERs). Four of the 11 economic evaluations presented models for patients in the first-line setting, and 7 presented models for patients in the relapsed/refractory (R/R) setting.. The majority of economic evaluations were conducted using a Markov model with 3-5 health states. R-Chemo was the most common comparator used in both the first line and relapsed/refractory settings. Across the 7 studies reporting costs or resource-use data, all 7 reported data for resource-use and 3 additionally reported costs data. There were a variety of costs and resource use data reported, including treatment-specific and non-treatment-specific data. Studies reported adverse events (AEs) as key drivers of increased costs and resource use. One study specifically reported statistically significant (p≤0.005) increases in emergency room visits were associated with MCL disease related AEs (odds ratio [OR]: 10.571). The following disease-specific HRQoL measures were reported: FACT-Lym, FACT-G, and EORTC QLQ-C30. There was little consistency in the measures used to evaluate HRQoL across studies. Table 2 presents the 2 studies reporting FACT-Lym scores. In both studies, trends for improvement in FACT-Lym total scores following treatment were reported. One phase 3 randomized study in R/R MCL reported 66% of ibrutinib-treated patients and 48% of temsirolimus-treated patients achieving a clinically meaningful improvement in FACT-Lym score. A second study in front line MCL reported improvements in the FACT-Lym total score following treatment with lenalidomide + rituximab. Each of these studies also demonstrated that clinical response to treatment was associated with the improvement in overall HRQoL. Conclusions These SLRs highlight the limited availability of published economic and HRQoL evidence for patients with MCL. The paucity of evidence is even more evident when first-line and R/R data are examined separately. Markov models with 3-5 health states represented the majority of economic evaluations . In both the first line and relapsed/refractory settings, R-Chemo was the most common comparator used. For both settings, AEs may have significant effects on the economic burden MCL places on healthcare payers. Novel agents have shown a clinically meaningful improvement in HRQoL. The noted economic burden of the disease demonstrates a need for newer treatments that decrease the burden MCL places on health care systems globally. There remains a need for future research to further understand the economic and HRQoL burden of MCL. Disclosures Monga: Janssen Pharmaceutica NV: Employment. Garside:Janssen Pharmaceutica NV: Employment. Davids:Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; AbbVie, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; MEI Pharma: Consultancy, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Roche/Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy; Surface Oncology: Research Funding. Tam:Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Research Funding; BeiGene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Ward:Janssen Pharmaceutica NV: Consultancy. Fotheringham:Janssen Pharmaceutica NV: Consultancy. O'Donovan:Janssen Pharmaceutica NV: Consultancy. Parisi:Janssen: Employment. Tapprich:Janssen Pharmaceutica NV: Employment.