Rituximab for the treatment of relapsed or refractory stage III or IV follicular non-Hodgkin's lymphoma

Abstract

This paper presents a summary of the evidence review group report into the clinical effectiveness and cost-effectiveness of rituximab for the treatment of relapsed or refractory stage III or IV follicular non-Hodgkin's lymphoma (NHL), in accordance with the licensed indication, based upon the evidence submission from Roche Products Ltd to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submitted clinical evidence included two randomised controlled trials [European Organisation for Research and Treatment of Cancer (EORTC) and German Low Grade Lymphoma Study GroupFludarabine, Cyclophosphamide and Mitoxantrone and (GLSG-FCM)] comparing the clinical effects of chemotherapy with or without rituximab in the induction of remission at first or second relapse and the clinical benefits of rituximab maintenance therapy versus the NHS's current clinical practice of observation for follicular lymphoma (FL) patients. Both trials showed that in patients with relapsed FL the addition of rituximab to chemotherapy induction treatment increased overall response rates. Furthermore, rituximab maintenance therapy increased the median length of remission when compared with observation only. Safety data from the two trials showed that while the majority of patients reported some adverse events, the number of patients withdrawing from treatment in the EORTC trial was low, with rates not being reported for the GLSG-FCM trial. Discussion of ERG reports is invited. Visit the HTA website correspondence forum (www.hta.ac.uk/ correspond). DOI: 10.3310/hta13suppl2/06 Rituximab for the treatment of relapsed or refractory stage III or IV follicular non-Hodgkin's lymphoma 42The most commonly reported adverse events were blood/bone marrow toxicity, skin rashes and allergies. The ERG reran the manufacturer's economic model after altering several of the assumptions and parameter values in order to recalculate the cost-utility ratios, quality-adjusted life-years (QALYs) and estimates of benefits. The manufacturer reported that maintenance therapy with rituximab was cost-effective compared with observation against commonly applied thresholds, with an incremental cost-effectiveness ratio of £7721 per QALY gained. The greatest clinical effectiveness is achieved by R-CHOP followed by rituximab maintenance (R-CHOP>R) and this treatment strategy had the greatest probability of being cost-effective for a QALY of approximately £18,000 or greater. The guidance issued by NICE as a result of the STA states that in people with relapsed stage III or IV follicular NHL, rituximab is now an option in combination with chemotherapy to induce remission or alone as maintenance therapy during remission. Rituximab monotherapy is also an option for people with relapsed or refractory disease when all alternative treatment options have been exhausted.

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

“…To demonstrate the flexibility/adaptability of the generic model developed in the current study, we tested two scenarios based on NICE guidelines and explored their annual economic impacts on the health care system using effect sizes reported in clinical trials [4] , [34] , which may or may not be generalizable to the patient population as a whole. In this context, the model performed well, producing results that are broadly consistent with the findings from relevant trial-based literature, although the costs for both scenarios were on the lower side [10] , [11] , [14] , [16] , [18] , [20] , [21] , [22] . In addition, although both scenarios demonstrated expected savings, wider dispersion of annual economic impact was observed in Scenario 2.…”

“…In recent years, a number of economic studies have been carried out in FL treatment trials [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] . The majority of these have focused on comparing the cost-effectiveness of administering the monoclonal antibody rituximab at particular points along the patient pathway, either in combination with chemotherapy (immunochemotherapy) both as first-line therapy and subsequently for relapsed/refractory disease, or alone (monotherapy) either as frontline in the W&W phase or as maintenance during remission [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] . However, the findings from such studies can provide only limited information to policymakers, not only because they relate to selected patients at specific points in time but also because certain groups, such as those treated palliatively and those whose disease transforms to DLBCL, are excluded [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] .…”

Psychological advocacy toward healing (PATH): study protocol for a randomized controlled trial

“…An effect size in the 0.4 to 0.5 range is also comparable to the outcome of trials of psychological interventions for women who have experienced domestic violence (see Appendix 7.5 in our systematic review of interventions [38]). For example, Kubany and colleagues’ two trials of CBT for women diagnosed with PTSD following intimate partner violence reported effect sizes of 0.9 [19] and 0.33 [18], respectively, for PTSD and 0.4 and 0.25, respectively, for depression outcomes.…”

Symptom burden and quality of life in patients with follicular lymphoma undergoing maintenance treatment with rituximab compared with observation

“…Response duration in the treatment of FL is improving [Boland et al 2009;Cheung et al 2009;Friedberg et al 2009;Fisher et al 2005], due in part to treatment advances such as the introduction of rituximab, and the clinical benefits of rituximab maintenance [Maloney, 2008;Forstpointner et al 2006]. However, physicians continue to balance treatment decisions with the potential impact on patient HRQoL.…”