Budget Impact of Introducing Fixed-Duration Mosunetuzumab for the Treatment of Relapsed or Refractory Follicular Lymphoma After Two or More Lines of Systemic Therapy in the USA.

OBJECTIVE: This study aimed to assess the budget impact of introducing fixed-duration mosunetuzumab as a treatment option for adult patients with relapsed or refractory follicular lymphoma after at least two prior systemic therapies and to estimate the total cumulative costs per patient in the USA. METHODS: A 3-year budget impact model was developed for a hypothetical 1-million-member cohort enrolled in a mixed commercial/Medicare health plan. Comparators were: axicabtagene ciloleucel, tisagenlecleucel, tazemetostat, rituximab plus lenalidomide, copanlisib, and older therapies (rituximab or obinutuzumab ± chemotherapy). Costs per patient comprised treatment-associated costs including the drug, its administration, adverse events, and routine care. Dosing and safety data were ascertained from respective package inserts and clinical trial data. Drug costs (March 2023) were estimated based on the average wholesale acquisition cost reported in AnalySource®, and all other costs were based on published sources and inflated to 2022 US dollars. Market shares were obtained from Genentech internal projections and expert opinion. Budget impact outcomes were presented on a per-member per-month basis. RESULTS: Compared with a scenario without mosunetuzumab, its introduction over 3 years resulted in a budget increase of $69,812 (1% increase) and an average per-member per-month budget impact of $0.0019. Among the newer therapies, mosunetuzumab had the second-lowest cumulative per patient cost (mosunetuzumab = $202,039; axicabtagene ciloleucel = $505,845; tisagenlecleucel = $476,293; rituximab plus lenalidomide = $263,520; tazemetostat = $250,665; copanlisib = $127,293) and drug costs, and its introduction only increased total drug costs by 0.1%. By year 3, the cumulative difference in the per patient cost with mosunetuzumab was -$303,805 versus axicabtagene ciloleucel, -$274,254 versus tisagenlecleucel, -$61,481 versus rituximab plus lenalidomide, -$48,625 versus tazemetostat, and $74,747 versus copanlisib. Older therapies were less costly with 3-year cumulative costs that ranged from $36,512 to $147,885. CONCLUSIONS: Over 3 years, the estimated cumulative per patient cost of mosunetuzumab is lower than most available newer therapies, resulting in a small increase in the budget after its formulary adoption for the treatment of relapsed or refractory follicular lymphoma.

Economic burden and treatment patterns for patients with diffuse large B-cell lymphoma and follicular lymphoma in the USA.

AIM: Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are common types of non-Hodgkin's lymphoma, and real-world evidence continues to be lacking for healthcare costs and utilization among DLBCL and FL patients. Our study aims to describe medical and pharmacy costs and health resource utilization and to characterize longitudinal treatment patterns among these patients. METHODS: A retrospective observational study was performed among adult patients with DLBCL or FL using the US MarketScan (Truven) administrative claims data from 1 January 2007 to 31 December 2015. Diagnoses of DLBCL and FL were based upon ICD-9 codes. Identifications of treatment lines involved 30 lymphoma-specific anticancer systemic agents. Direct healthcare costs and utilizations were computed in the 1-year postdiagnosis period. Generalized linear models with a gamma link were used to compare healthcare costs between therapies with and without rituximab. RESULTS: A total of 2767 DLBCL and 5989 FL patients received frontline therapy. The majority received treatment within 3 months after initial diagnosis (DLBCL 79.9% and FL 62.4%) and were treated with rituximab or bendamustine either alone or in combination (DLBCL 67.4% and FL 84.7%). The total healthcare costs were US $15,555 and $10,192 per patient per month within 1 year following their initial diagnosis for DLBCL and FL, respectively. The medical costs were nearly twice as much as the drug costs for DLBCL patients. Both DLBCL and FL patients receiving rituximab had higher pharmacy costs but lower medical costs (p < 0.001). During the first year following initial diagnosis, the resource utilization (per patient per month) of DLBCL patients included 0.21 inpatient admissions, 0.26 radiation therapy, 2.63 outpatient or office visits, 0.18 emergency room visits, 0.06 intensive care unit admissions and 0.10 stem cell transplantation. FL patients occupied less health resources than DLBCL patients. CONCLUSION: The healthcare costs and health resources utilized were considerable in non-Hodgkin's lymphoma, especially DLBCL patients.

Obinutuzumab plus chemotherapy followed by obinutuzumab monotherapy is cost-effective vs. rituximab plus chemotherapy followed by rituximab monotherapy for previously untreated follicular lymphoma patients in the United States.

The GALLIUM trial compared obinutuzumab (GA101, G)-based chemotherapy followed by G monotherapy (G + chemo) for up to two years to rituximab (R)-based chemotherapy followed by R monotherapy (R + chemo) for up to two years in previously untreated follicular lymphoma (FL) patients. We estimated the cost-effectiveness of G + chemo versus R + chemo utilizing GALLIUM trial data and published literature. G + chemo had increased drug costs (undiscounted: $135,200 versus $127,700 for R + chemo), representing a relative increase of 5.9%. However, this was offset by a $6,400 lower cost for disease progression. G + chemo led to increased quality-adjusted life years (QALYs) relative to R + chemo of 0.81 (95% credible range, [CR]: 0.22-1.37), and the overall discounted incremental cost was $1,900 (95% CR: -$7,400 to $8,900). The incremental cost-effectiveness ratio was ∼$2,300 per QALY gained, and the results were highly robust to sensitivity analyses. Treatment with G + chemo compared to R + chemo is cost-effective in previously untreated FL patients in the US.

Burden of illness of follicular lymphoma and marginal zone lymphoma.

Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are two subtypes of indolent B cell non-Hodgkin lymphoma (NHL) that account for approximately 20% and 12% of all NHLs, respectively. FL and MZL are rare conditions with orphan disease designations. We conducted a comprehensive review of the burden of FL and MZL that encompasses the epidemiological, real world clinical, economic, and humanistic impact of these diseases globally. A targeted literature search identified 31 eligible studies for review. Epidemiological coverage was poor, with data obtained for studies from only seven countries. The incidences of both subtypes were low: age-standardized incidence rates of FL ranged from 2.1/100,000 in France to 4.3/100,000 in the USA, while for MZL it varied geographically from 0.5/100,000 in Australia to 2.6/100,000 in the UK. The cumulative total direct healthcare costs for FL were higher for patients with progressive disease compared to those without ($30,890 vs. $8704 at 12 months, respectively) and main driver of costs related to the use of chemotherapy. Five-year overall survival was improved in patients with FL compared with MZL (e.g., 76.5% vs 60.7% in one study that reported on both subtypes). Mortality rates were particularly lower in female patients with FL aged < 60 years. However, limited outcome data for MZL patients were identified. FL and MZL contribute significant burden on healthcare systems and on patients globally, with delays in progression potentially leading to cost savings. More rigorous characterization of these two NHL subtypes, new and more effective treatments, and standardization of reporting would lead to a more robust understanding of future data in this disease area.

Obinutuzumab in Combination with Chemotherapy for the First-Line Treatment of Patients with Advanced Follicular Lymphoma : An Evidence Review Group Evaluation of the NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence (NICE), as part of the institute's single technology appraisal (STA) process, invited the company that makes obinutuzumab (Roche Products Limited) to submit evidence of the clinical and cost effectiveness of the drug in combination with chemotherapy, with or without obinutuzumab as maintenance therapy for adult patients with untreated, advanced follicular lymphoma (FL) in the UK. Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Erasmus University Rotterdam, was commissioned to act as the Evidence Review Group (ERG). This paper describes the company's submission, the ERG review, and NICE's subsequent decisions. The clinical evidence was derived from two phase III, company-sponsored, randomised, open-label studies. Most evidence on obinutuzumab was based on the GALLIUM trial that compared obinutuzumab in combination with chemotherapy as induction followed by obinutuzumab maintenance monotherapy with rituximab in combination with chemotherapy as induction followed by rituximab maintenance monotherapy in previously untreated patients with FL (grades 1-3a). Long-term clinical evidence was based on the PRIMA trial, studying the benefit of two years of rituximab maintenance after first-line treatment in patients with FL. The cost-effectiveness evidence submitted by the company relied on a partitioned survival cost-utility model, implemented in Microsoft® Excel. The base-case incremental cost-effectiveness ratio (ICER) presented in the company submission was <£20,000 per quality-adjusted life-year (QALY) gained. Although the ERG concluded that the economic model met the NICE reference case to a reasonable extent, some errors were identified and several assumptions made by the company were challenged. A new base-case scenario produced by the ERG suggested an ICER that was higher than the company base case, but still below £30,000 per QALY gained. However, some ERG scenario analyses were close to or even above the threshold. This was the case in particular for assuming a treatment effect that did not extend beyond trial follow-up. These results led to an initial negative recommendation by the appraisal committee. Subsequently, the company submitted a revised base case focusing on patients at intermediate or high risk of premature mortality. Simultaneously, a further price discount for obinutuzumab was granted. In addition to the company's revised base case, the ERG suggested a restriction of the treatment effect to 5 years and implemented biosimilar uptake and cheaper prices for rituximab. All of these adjustments did not exceed £30,000 per QALY gained and therefore the use of obinutuzumab for patients with advanced FL and a Follicular Lymphoma International Predictive Index (FLIPI) score of two or more could be recommended.

Evaluation of subcutaneous rituximab administration on Canadian systemic therapy suites.

Background: Non-Hodgkin lymphoma (nhl) is the most common hematologic malignancy. Diffuse large B-cell lymphoma (dlbcl) and follicular lymphoma (fl) constitute 55% of new nhl cases and are initially treated with rituximab-based chemoimmunotherapy. Relative to intravenous (IV) rituximab, a subcutaneous (sc) formulation approved in 2016 has comparable pharmacokinetics, efficacy, and safety, and a greatly reduced administration time; it is also preferred by patients. The objective of the present study was to estimate the effect (on systemic therapy suite time and on the costs of drug acquisition and administration) of implementing sc rituximab in the initial chemoimmunotherapy for fl and dlbcl over 3 years in the Canadian market. Methods: An Excel (Microsoft Corporation, Redmond, WA, U.S.A.)-based model was created with a population size based on epidemiologic data and current rituximab use, duration of use considering initial therapy, time savings for sc rituximab administration from published studies, costs from standard Canadian sources, and assumed uptake in implementing provinces of 65%, 75%, and 80% over 3 years. Key parameters and sensitivity analysis values were validated by clinical experts located in various Canadian jurisdictions. Costs are reported in 2017 Canadian dollars from the perspective of the health care system. Results: More than 3 years after implementation of sc rituximab, we estimated that 5762 Canadians would be receiving sc rituximab, resulting in savings of 128,715 hours in systemic therapy suite time and approximately $40 million in drug and administration costs. Sensitivity analyses suggest that the model is most sensitive to sc market uptake, number of induction therapy cycles, and eligible patients. Conclusions: Subcutaneous administration of rituximab can significantly reduce systemic therapy suite time and achieve substantial savings in drug and administration costs.

A Generic Model for Follicular Lymphoma: Predicting Cost, Life Expectancy, and Quality-Adjusted-Life-Year Using UK Population-Based Observational Data.

OBJECTIVES: To use real-world data to develop a flexible generic decision model to predict cost, life expectancy, and quality-adjusted life-years (QALYs) for follicular lymphoma (FL) in the general patient population. METHODS: All patients newly diagnosed with FL in the UK's population-based Haematological Malignancy Research Network (www.hmrn.org) between 2004 and 2011 were followed until 2015 (N = 740). Treatment pathways, QALYs, and costs were incorporated into a discrete event simulation to reflect patient heterogeneity, including age and disease management. Two scenario analyses, based on the latest National Institute for Health and Clinical Excellence (NICE) guidelines (rituximab induction therapy for newly diagnosed asymptomatic patients and rituximab maintenance therapy for patients between treatments), were conducted and their economic impacts were compared to current practice. RESULTS: Incidence-based analysis revealed expected average lifetime costs ranging from £6,165 [US$7,709] to £63,864 [US$79,862] per patient, and average life expectancy from 75 days to 17.56 years. Prevalence-based analysis estimated average annual treatment costs of £60-65 million [US$75-80 million], accounting for approximately 10% of the United Kingdom's annual National Health Service budget for hematological cancers as a whole. Assuming that treatment effects reported in trials are applicable to all patient groups, scenario analyses for two recent NICE guidelines demonstrated potential annual cost savings for the United Kingdom that ranged with uptake frequency from £0.6 million to £11 million [US$0.75-2.75 million]. CONCLUSIONS: Costs, survival, and QALYs associated with FL vary markedly with patient characteristics and disease management. Allowing the production of more realistic outcomes across the patient population as a whole, our model addresses this heterogeneity and is a useful tool with which to evaluate new technologies/treatments to support healthcare decision makers.

Cost-Effectiveness of Obinutuzumab in Combination with Bendamustine Followed by Obinutuzumab Maintenance versus Bendamustine Alone in Treatment of Patients with Rituximab-Refractory Follicular Lymphoma in Norway.

AIMS: To evaluate the cost-effectiveness of obinutuzumab in combination with bendamustine followed by obinituzumab maintenance (Obin-Benda) compared to bendamustine alone (Benda) in patients with refractory follicular lymphoma (FL) in a Norwegian setting. METHODS: A three-state area-under-the-curve (AUC) model was developed. The states included were progression-free-survival (PFS), progressed disease (PD), and death. Each state had costs and utilities assigned to it. The pivotal phase III randomized controlled trial GADOLIN was used for clinical input in the model along with Norwegian cost estimates. The trial demonstrated that Obin-Benda improved overall survival (OS), with a hazard ratio (HR) of 0.67 (95% CI 0.47-0.96), and reduced the likelihood of progression or death (HR 0.52, 95% CI 0.39-0.69) compared to Benda. The model used EQ-5D data collected in the GADOLIN trial, with UK tariffs assigned to the EQ-5D scores. RESULTS: The total quality adjusted life-years (QALYs) for the patients on Obin-Benda were estimated to be 4.67, compared to 3.65 for Benda, while the total costs were estimated to be €98,849 and €51,570, respectively. Obin-Benda had an incremental gain of 1.02 QALYs compared to Benda, at an additional cost of €47,279. The estimated deterministic incremental cost-effectiveness ratio (ICER) was €46,438 per QALY gained, while the probabilistic ICER was €46,887 per QALY gained (95% CI €34,772-€59,443). The results were robust to changes in various sensitivity and scenario analyses. CONCLUSIONS: The cost-effectiveness threshold in Norway is not public, but based on previous decisions it is estimated to be up to approximately €89,000 per QALY (NOK 800,000). The results of the analysis indicate that obinutuzumab in combination with bendamustine followed by obinutuzumab maintenance may be cost-effective compared to bendamustine alone in Norway.

Economic burden of patients with diffuse large B-cell and follicular lymphoma treated in the USA.

AIM: Evaluate healthcare costs and utilization of treated diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) patients. MATERIALS & METHODS: Adults with newly diagnosed DLBCL and FL between 1 January 2008 and 31 October 2015 were identified in the Optum™ claims database. Healthcare costs and utilization were assessed from diagnosis date until end of follow-up. RESULTS: A total of 1267 DLBCL- and 1595 FL-treated patients were identified. Mean per-patient, per-month cost during follow-up was US$11,890 for DLBCL and US$10,460 for FL. Healthcare costs and utilization decreased from year 1 to 2 following diagnosis, due to a decrease in chemotherapy services, inpatient admissions and other outpatient services. CONCLUSION: The economic burden of treated DLBCL and FL is considerable, especially in the first year following diagnosis.

SMABcare study: subcutaneous monoclonal antibody in cancer care: cost-consequence analysis of subcutaneous rituximab in patients with follicular lymphoma.

Rituximab is used as a standard of care for follicular lymphoma and is usually administered intravenously. A novel subcutaneous formulation recently showed non-inferior efficacy with similar pharmacokinetic and safety profiles compared to intravenous rituximab in patients with follicular lymphoma. This new approach is promising in terms of comfort for patients and time-saving for hospital staff. To evaluate the real-life economic impact of subcutaneous rituximab as maintenance therapy in patients with follicular lymphoma in real life, we conducted a cost-consequence analysis from the hospital's point of view in three French teaching hospitals. Health-related quality of life (EQ-5D-3L) was investigated as well as patients' and nurses' perception. Compared to intravenous rituximab, subcutaneous administration showed an estimated cost-saving of €109.20 per patient per cycle (p < 0.001), 78.6% of which could be attributed to the rituximab cost. Health-related quality of life showed no significant difference between the two groups despite tendencies for greater pain in the subcutaneous group and greater anxiety in the intravenous group. Thus, subcutaneous rituximab had a favorable pharmacoeconomic profile, with clinical efficacy similar to that of intravenous rituximab. The subcutaneous form was preferred by almost all patients, but further consideration should be given to improve the patients' experience: a dedicated day unit with trained medical, nursing, and pharmaceutical staff could be helpful.

Retrospective analysis of first-line treatment for follicular lymphoma based on outcomes and medical economics.

BACKGROUND: Follicular lymphoma (FL) is the most common type of non-Hodgkin lymphoma (NHL), with indolent progression. Several treatment options are selected, based not only on disease status, quality of life (QOL), and age of patient, but also on recent increasing medical costs. We retrospectively analysed the first-line treatment of FL with regard to treatment outcomes and medical economics, and discuss the appropriate strategies for FL. METHODS: Data on a total of 69 newly-diagnosed patients with FL was retrospectively collected from 2001 to 2015. RESULTS: The median age of the patients was 60 years and the median follow-up was 58 months. A total of 25 cases with FL were treated with R monotherapy, and 28 cases were treated with R-CHOP as first-line treatment. The factors affecting the decision of physicians to use R or R-CHOP treatment were serum level of lactate dehydrogenase (LDH) and disease stage. The first-line treatment-associated survival did not show any statistical differences between R and R-CHOP. The average hospitalization and average of all medical costs during the first-line treatment were 4.1 days (R) versus 55.7 days (R-CHOP), and JPY 1,707,693 (USD 15,324) (R) versus JPY 2,136,117 (USD 19,170) (R-CHOP), respectively. CONCLUSION: R monotherapy for patients whose diseases show low tumor burden and who are not candidates for local treatment has benefits as a first-line treatment compared to R-CHOP, based on the patients' QOL and medical economics.

Cost-Effectiveness Analysis of Bendamustine Plus Rituximab as a First-Line Treatment for Patients with Follicular Lymphoma in Spain.

BACKGROUND: Follicular lymphoma (FL) is the second most common type of lymphoid cancer in Western Europe. OBJECTIVE: The aim of this study was to evaluate the cost utility of rituximab-bendamustine treatment compared with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) treatment as a first-line therapy for patients with advanced FL in Spain. METHODS: A Markov model was developed to estimate the cost effectiveness of rituximab-bendamustine compared with R-CHOP as first-line treatment for patients with advanced FL in the Spanish National Health System (NHS). Transitions between health states (progression-free, including induction and maintenance; first relapse; second relapse; and death) were allowed for the patient cohort in 4-week-long cycles. Clinical data for the extrapolation of progression-free survival curves were obtained from randomized trials. Mortality rates and utilities were obtained from the literature. Outcomes were measured as quality-adjusted life-years (QALYs). The total costs (€, 2013) included drug costs (ex-factory prices with mandatory deductions), disease management costs and adverse event-associated costs. Costs and outcomes were discounted at a 3 % annual rate. Probabilistic sensitivity analysis was performed using 10,000 Monte Carlo simulations to assess the model robustness. RESULTS: Treatment and administration costs during the induction phase were higher for rituximab-bendamustine (€17,671) than for R-CHOP (€11,850). At the end of the 25-year period, the rituximab-bendamustine first-line strategy had a total cost of €68,357 compared with €69,528 for R-CHOP. Health benefits were higher for rituximab-bendamustine treatment (10.31 QALYs) than for R-CHOP treatment (9.82 QALYs). In the probabilistic analysis, rituximab-bendamustine was the dominant strategy over treatment with R-CHOP in 53.4 % of the simulations. CONCLUSION: First-line therapy with rituximab-bendamustine in FL patients was the dominant strategy over treatment with R-CHOP; it showed cost savings and higher health benefits for the Spanish NHS.

Frontline rituximab monotherapy induction versus a watch and wait approach for asymptomatic advanced-stage follicular lymphoma: A cost-effectiveness analysis.

BACKGROUND: A watch and wait (WW) strategy is the standard of care for patients with asymptomatic advanced-stage follicular lymphoma. Recent data have demonstrated an improvement in the time to progression with rituximab induction (RI) with or without rituximab maintenance (RM) in comparison with a WW strategy wait in such patients. It remains unclear whether this is a cost-effective strategy. METHODS: A Markov decision analysis model was developed to compare the clinical outcomes, costs, and cost-effectiveness of RI (4 weekly doses) plus RM (12 doses every 2 months), RI (4 weekly doses), and a WW strategy for patients newly diagnosed with low-burden, asymptomatic advanced-stage follicular lymphoma over a lifetime horizon. Baseline probabilities and utilities were derived from a systematic review of published studies, and they were evaluated on a 6-month cycle. A Canadian public health payer's perspective was adopted, and costs were presented in 2012 Canadian dollars. RESULTS: RI was the cheapest strategy. It was less costly at $59,953 versus $67,489 for the RM arm and $75,895 for the WW arm. It was also associated with a slightly lower quality-adjusted life expectancy at 6.16 quality-adjusted life years (QALYs) versus 6.28 QALYs for the RM strategy but was superior to WW (5.71 QALYs). In sensitivity analyses of key variables, this effectiveness was sensitive to the probability of first and second progression in the RI arm, and this indicated relatively neutral effectiveness between the 2 rituximab arms. CONCLUSIONS: RI without maintenance for asymptomatic advanced-stage follicular lymphoma is the preferred strategy: it minimizes costs per patient over a lifetime horizon.

Comparing the cost-effectiveness of rituximab maintenance and radioimmunotherapy consolidation versus observation following first-line therapy in patients with follicular lymphoma.

BACKGROUND: Phase 3 randomized trials have shown that maintenance rituximab (MR) therapy or radioimmunotherapy (RIT) consolidation following frontline therapy can improve progression-free survival for patients with follicular lymphoma (FL), but the cost-effectiveness of these approaches with respect to observation has not been examined using a common modeling framework. OBJECTIVES: To evaluate and compare the economic impact of MR and RIT consolidation versus observation, respectively, following the first-line induction therapy for patients with advanced-stage FL. METHODS: We developed Markov models to estimate patients' lifetime costs, quality-adjusted life-years (QALYs), and life-years (LYs) after MR, RIT, and observation following frontline FL treatment from the US payer's perspective. Progression risks, adverse event probabilities, costs, and utilities were estimated from clinical data of Primary RItuximab and MAintenance (PRIMA) trial, Eastern Cooperative Oncology Group (ECOG) trial (for MR), and First-line Indolent Trial (for RIT) and the published literature. We evaluated the incremental cost-effectiveness ratio for direct comparisons between MR/RIT and observation. Model robustness was addressed by one-way and probabilistic sensitivity analyses. RESULTS: Compared with observation, MR provided an additional 1.089 QALYs (1.099 LYs) and 1.399 QALYs (1.391 LYs) on the basis of the PRIMA trial and the ECOG trial, respectively, and RIT provided an additional 1.026 QALYs (1.034 LYs). The incremental cost per QALY gained was $40,335 (PRIMA) or $37,412 (ECOG) for MR and $40,851 for RIT. MR and RIT had comparable incremental QALYs before first progression, whereas RIT had higher incremental costs of adverse events due to higher incidences of cytopenias. CONCLUSIONS: MR and RIT following frontline FL therapy demonstrated favorable and similar cost-effectiveness profiles. The model results should be interpreted within the specific clinical settings of each trial. Selection of MR, RIT, or observation should be based on patient characteristics and expected trade-offs for these alternatives.

Cost-effectiveness of rituximab as maintenance treatment for relapsed follicular lymphoma: results of a population-based study.

OBJECTIVES: On the basis of two population-based registries, our study aims to calculate the real-world cost-effectiveness of rituximab maintenance compared with observation in relapsed or refractory follicular lymphoma patients who responded to second-line chemotherapy. METHODS: Data were obtained from the EORTC20981 trial, the Netherlands Cancer Registry and two population-based registries. A Markov model was developed to calculate cost per life year gained (LYG) and quality-adjusted life years (QALYs) for three scenarios. RESULTS: Our real-world patients were (62 years) 6 to 7 years older and had higher complete response rates to second-line chemotherapy than the trial population. Differences between the real-world rituximab and observation group were observed for second-line chemotherapy and disease progression. Groups were more balanced after using propensity matching. Relying entirely on updated trial results (scenario1) in combination with local cost data resulted in ratios of €11,259 per LYG and €12,655 per QALY. For scenario2, consisting of trial efficacy and matched real-world costs, ratios of €21,202 per LYG and €23,821 per QALY were calculated. Using real-world matched evidence (scenario3) for both effectiveness and costs showed ratios of €10,591 per LYG and €11,245 per QALY. CONCLUSION: Although differences in real-world and trial population were found, using real-world data as well as results from long-term trial follow-up showed favourable ICERs for rituximab maintenance. Nevertheless, results showed that caution is required with data synthesis, interpretation and generalisability of results. As different scenarios provide answers to different questions, we recommend healthcare decision-makers to recognise the importance of calculating several cost-effectiveness scenarios.

Rituximab for the first-line maintenance treatment of follicular non-Hodgkin's lymphoma : a NICE single technology appraisal.

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of rituximab (RTX) [Roche] to submit evidence for the clinical and cost effectiveness of RTX as first-line maintenance treatment for patients with follicular non-Hodgkin's lymphoma (fNHL) whose disease has responded to induction therapy with RTX plus cytotoxic chemotherapy (R-CTX) in accordance with the Institute's Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article summarizes the ERG's review of the evidence submitted by the manufacturer and provides a summary of the Appraisal Committee's (AC) decision. The clinical evidence was derived from a multi-centred, open-label, randomized phase III study (PRIMA) comparing first-line maintenance treatment with RTX with observation only in 1,018 patients with previously untreated advanced fNHL. Median time to event (MTE) for the primary endpoint of progression-free survival (PFS) in the RTX arm was not estimable due to data immaturity; median PFS in the observation arm was 48.36 months. A statistically significant benefit of RTX maintenance therapy for PFS was reported (hazard ratio [HR] 0.55, 95 % CI 0.44-0.68; p < 0.0001). Statistically significant differences in favour of RTX were also reported for a range of secondary endpoints. Assessment of overall survival benefit could be not made due to insufficient events. The ERG's main concern with the clinical-effectiveness data presented was their lack of maturity. The submitted incremental cost-effectiveness ratio was within the NICE threshold. The ERG questioned the model on a number of grounds, particularly the use of Markov methodology rather than patient simulations, the impact of patient age on the outcome and the projective PFS modelling. The ERG considered it impossible to draw firm conclusions regarding the clinical or cost effectiveness of the intervention as the dataset was as yet too immature. At a third meeting, the AC concluded that RTX could be recommended as first-line maintenance treatment for patients with fNHL whose disease has responded to induction R-CTX.

Rituximab maintenance versus retreatment in follicular lymphoma.

Follicular lymphoma (FL) is the most common type of indolent non-Hodgkin lymphoma. Although the introduction of the anti-CD20 monoclonal antibody rituximab has represented a major breakthrough, FL remains incurable with standard chemoimmunotherapies. The goals of therapy in symptomatic FL patients include the following: obtaining high response rates, extending the duration of remission, prolongation of survival and improving quality of life, while minimizing adverse events. To extend remission duration and possibly survival outcomes, maintenance therapy with rituximab has been shown to be effective in both frontline and relapsed/refractory settings. However, the optimal timing, schedule and length of maintenance therapy are controversial. Herein, we review the current data for maintenance rituximab in FL, discuss the current controversies for this modality, attempt to define its role relative to the more conservative retreatment approach and provide practical recommendations for its clinical use.

Cost-effectiveness of rituximab in follicular lymphoma.

In advanced follicular lymphoma, rituximab is currently used with chemotherapy as induction therapy, and as maintenance monotherapy following induction in previously untreated patients and treatment-experienced relapsed/refractory patients. Herein, the authors characterize the clinical effectiveness, safety and cost-effectiveness of rituximab in follicular lymphoma, based on the literature review. Rituximab has a favorable safety profile and has been shown to improve progression-free survival, with some evidence of improvements to overall survival, particularly for relapsed/refractory patients. Rituximab has consistently been found to have a favorable economic profile, with cost per quality-adjusted life year falling within standard thresholds for cost-effectiveness. Challenges in cost-effectiveness analysis include the fact that life expectancy for patients with follicular lymphoma exceeds the period of available follow-up data and that treatment pathways are more complex than the model structures frequently used in oncology models. As data accrue and more complex models are developed, the cost-effectiveness of rituximab can be more accurately assessed.

[Cost-effectiveness analysis of maintenance therapy with rituximab in patients with follicular lymphoma responding to induction therapy at the first line]. / Análisis coste-efectividad del tratamiento de mantenimiento con rituximab en pacientes con linfoma folicular que responden a la terapia de inducción en primera línea.

BACKGROUND: Maintenance therapy with rituximab for follicular lymphoma (FL) responding to induction at the first-line, significantly increases progression-free survival compared with observation. To estimate the efficiency of this therapeutic option, we performed a cost-effectiveness analysis of maintenance therapy of the follicular lymphoma (FL) that responds to induction in first line, with rituximab, compared with the option of "watch and wait" strategy. METHODS: We did a Markov model of the FL, with four health states (progression free survival in first or second line, progression and death). The transition probabilities between states were obtained from clinical trials PRIMA and EORTC 20981. Health state utilities were obtained from literature. The use of health resources, from the perspective of the National Health System was estimated by a panel of Spanish clinical experts. Unit costs (euros in 2011) were obtained from Spanish sources. Deterministic and probabilistic analyses were made. RESULTS: In the deterministic base case analysis, for a time horizon of 30 years, the cost per life year gained (LYG) and quality-adjusted life-years (QALYs) gained, was euros 5,663 and euros 6,253 respectively. The sensitivity analyses confirmed the stability of the base case for time horizons of 10 and 20 years and various statistical distributions (Weibull, exponential, log-logistic, log-normal, Gompertz, and gamma) ranging between euros 4,222 and euros 8,766. Rituximab maintenance is cost-effective from a time horizon of 5.7 years (cost per QALY gained of euros 29,998). CONCLUSION: Compared with observation, rituximab maintenance treatment of the FL that responds to induction therapy in first line, is cost-effective according to the present model.