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

2009 ◽  
Vol 13 (Suppl 2) ◽  
pp. 41-48
Author(s):  
A Boland ◽  
A Bagust ◽  
J Hockenhull ◽  
H Davis ◽  
P Chu ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Adverse Events ◽  
Maintenance Therapy ◽  
Hodgkin’S Lymphoma ◽  
Clinical Effectiveness ◽  
Cost Effective ◽  
Hodgkin's Lymphoma ◽  
Stage Iii ◽  
Rituximab Maintenance ◽  
Non Hodgkin's Lymphoma

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 Group – Fludarabine, 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. The 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.

Cost-Effectiveness of Rituximab for Maintenance in Patients with Follicular Non-Hodgkin’s Lymphoma in the Dutch Setting

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2364-2364
Author(s):  
Marjolein Pompen ◽  
P.C. Huijgens
Keyword(s):  
Economic Evaluation ◽  
Cost Effectiveness ◽  
Maintenance Therapy ◽  
Incremental Cost ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Rituximab Maintenance ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
The Cost

Abstract <>Cost-Effectiveness of Rituximab For Maintenance in Patients With Follicular Non-Hodgkin’s Lymphoma in the Dutch setting <>Rituximab (MabThera®/Rituxan®), a chimeric anti-CD20 monoclonal antibody, has shown to be effective in the treatment of indolent and aggressive non Hodgkin’s lymphoma (NHL), including follicular lymphoma (FL). The purpose of the current economic evaluation was to estimate the cost-effectiveness of rituximab added in the maintenance setting for patients with relapsed/refractory FL. The cost-effectiveness of rituximab maintenance therapy in the Dutch healthcare system was assessed by economic modelling based on survival data from an EORTC/HOVON randomized clinical trial (EORTC20981/HOVON 39 NHL) in which patients with relapsed or refractory FL were randomized for maintenance rituximab vs no treatment after having responded to induction therapy. Utility values were obtained from a study in patients with FL using the EQ-5D York Tariff (unpublished). The primary endpoint was the incremental cost per quality adjusted life year (QALY) gained. A secondary endpoint was the incremental cost per life year gained (LYG). Only direct health care costs (drug acquisition, administration, adverse events, treatment at relapse, and routine surveillance) were included in the economic evaluation. Effects (QALYs and LYG) and costs accruing after the first year of the economic evaluation were discounted at the rate of 1.5% and 4% per annum, respectively. The economic evaluation was done by using a three state health state transition model. In this model, all patients start in the progression free (PFD) state with possible transitions to progressive disease (PD) or death (D). Progression free survival (PFS) and overall survival (OS) data were extrapolated over a period of 30 years with monthly cycles. Rituximab maintenance was more effective than observation in terms of both LYG and QALYs gained. The average discounted life expectancy in the rituximab group exceeded the observation group by 1.10 years (6.27 vs. 5.16); rituximab maintenance was associated with an additional 0.97 QALYs compared to observation. Total costs were €27,094 (euro 2006) higher in the rituximab group than the observation group and were largely due to the cost of the study drug and its administration. The incremental cost per QALY gained was €27,896 and the incremental cost per LYG was €24,564. The results from the EORTC20981/HOVON 39 NHL trial provide evidence of an incremental clinical benefit for rituximab maintenance therapy compared to ‘observation’ in patients with relapsed or refractory FL who have responded to CHOP or R-CHOP induction therapy. Subsequently, the results of the current economic modelling show that rituximab maintenance therapy has an incremental cost-effectiveness ratio of €27,896/QALY. The results were most sensitive to the duration of treatment benefit and the difference in treatment frequency and costs upon relapse between the two treatment groups. However, in all cases rituximab maintenance therapy remained a treatment that represents a cost-effective intervention. The economic analysis has shown to be adequately robust, hence it can be concluded that rituximab maintenance therapy in the Dutch setting is cost-effective.

scholarly journals Rituximab for the first-line treatment of stage III/IV follicular non-Hodgkin’s lymphoma

2009 ◽  
Vol 13 (Suppl 1) ◽  
pp. 23-28
Author(s):  
Y Dundar ◽  
A Bagust ◽  
J Hounsome ◽  
C McLeod ◽  
A Boland ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Stage Iii ◽  
Line Treatment ◽  
First Line ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
The Impact ◽  
First Line Treatment

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of rituximab for the first-line treatment of stage III/IV follicular non-Hodgkin’s lymphoma (FNHL) based upon the manufacturer’s submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The manufacturer’s scope restricts the intervention to rituximab in combination with CVP (cyclophosphamide, vincristine and prednisolone) (R-CVP); the only comparator used was CVP alone. The evidence from the one included randomised controlled trial (RCT) suggests that the addition of rituximab to a CVP chemotherapy regimen has a positive effect on the outcomes of time to treatment failure, disease progression, overall tumour response, duration of response and time to new lymphoma treatment in patients with stage III/IV FNHL compared with CVP alone. Adverse events were comparable between the two arms. This study was confirmed as the only relevant RCT. The economic analyses provided by the manufacturer were modelled using a three-state Markov model with with the health states being defined as progression-free survival (PFS), progressed (in which patients have relapsed) and death (which is an absorbing state). The model generated results for a cohort of patients with an initial age of 53 and makes no distinction between men and women. The model is basic in design, with several serious design flaws and key parameter values that are probably incompatible. Attempting to rectify the identified errors and limitations of the model did not increase the incremental cost-effectiveness ratio (ICER) above £30,000. Although the cost-effectiveness results obtained appear to be compelling in support of R-CVP compared with CVP for the trial population the results may not be so convincing for a more representative population. The results of the ERG analysis on the impact of age suggest that ICERs increase steadily with age, as the proportion of PFS that can be converted to overall survival (OS) is diminished by rising mortality rates in the general population. For the most extreme scenario (no OS gain) the ICER appears to remain below £30,000 per QALY gained. On balance the evidence indicates that R-CVP is more cost-effective than CVP. The guidance issued by NICE in July 2006 as a result of the STA states that rituximab within its licensed indication (in combination with cyclophosphamide, vincristine and prednisolone) is recommended as an option for the treatment of symptomatic stage III/IV follicular non-Hodgkin’s lymphoma in previously untreated patients.

Rituximab Maintenance Therapy in CD20+ B-Cell Non-Hodgkin’s Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4805-4805
Author(s):  
Sanja A. Trajkova ◽  
Lidija A. Cevreska ◽  
Irina Z. Panovska-Stavridis ◽  
Aleksandra Pivkova ◽  
Borce Georgievski ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
B Cell ◽  
Initial Treatment ◽  
Hodgkin’S Lymphoma ◽  
B Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Pharmacokinetic Data ◽  
Rituximab Maintenance ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Abstract Purpose: Clinical and pharmacokinetic data suggest that high serum concentrations of rituximab and prolonged exposure to rituximab are associated with higher response rates and improved quality of response. We used rituximab-maintenance therapy to target minimal residual disease, with the aim of increasing the duration of remissions achieved following initial treatment. Methods: During 2001–2005, 14 patients with CD20+ B-cell non-Hodgkin’s lymphoma (seven with diffuse large B cell lymphoma [DLBCL] and seven with follicular lymphoma [FL]) were enrolled in the study. Patients with DLBCL and FL were required to have a CR or PR, respectively, following initial treatment. The most common initial treatments were R-CHOP, R-FC or CHOP. Rituximab-maintenance therapy was administered as 375mg/m2 doses every 3 months for 2 years. Three patients with aggressive DLBCL were treated with high-dose chemotherapy/autologous stem-cell transplantation (HDT/ASCT) and received rituximab-maintenance therapy every 2 months for four doses in total. Results: Most patients had disease of Ann Arbor stage ≥ 3 (two FL patients stage I). In patients with DLBCL, median event-free and overall survivals were 22.1 months and 22.3 months, respectively, with the corresponding values being 20.6 months and 26.1 months in patients with FL. To date, 13 patients are in continuous clinical remission and only one patient has relapsed. Conclusions: Rituximab-maintenance therapy is effective and well tolerated in this setting. Recruitment for this study is ongoing and evaluation of a larger patient population, together with a longer follow-up, will determine whether this treatment approach has curative potential.

Review of Current Patterns of Treatment and Costs in Follicular Non-Hodgkin’s Lymphoma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4676-4676
Author(s):  
Talia S. Foster ◽  
Jeffrey D. Miller ◽  
Mark E. Boye ◽  
Mason W. Russell
Keyword(s):  
Cost Effectiveness ◽  
The Netherlands ◽  
Hodgkin’S Lymphoma ◽  
Cost Effective ◽  
Treatment Patterns ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
The Us ◽  
Economic Studies

Abstract Introduction Follicular non-Hodgkin’s lymphoma (FNHL) comprises about 15–30% of all incident NHL in developed countries. US SEER data show that the annual incidence rate per 100,000 persons is 3.0 and 1.3 (white and black males, respectively) and 2.7 and 0.9 (white and black females, respectively). Patients with this slow-growing malignancy may live for 10 years or more, but it is considered incurable with standard treatment. The common disease pattern is a series of relapses and remissions, with each relapse responding less to treatment, and each remission shorter than the preceding one. Little is known about patterns and costs of current treatment for FNHL. Methods. We conducted a systematic review of the English-language, MEDLINE-indexed literature on FNHL published during the 10-year period beginning in May 1997 and ending in May 2007. The following search algorithm was used, with keywords in the title or abstract: (nodular OR follicular) AND non-Hodgkin‘s AND lymphoma[ti] NOT PCR NOT „case reports“[pt]. Government and organization-sponsored websites also were searched using these keywords. No geographic restrictions were used. Results: Literature identified. We manually reviewed the initial search results of 375 articles to identify those relevant to this research on FNHL treatment patterns and costs. Authors of 16 primary research studies reported treatment patterns (5) and/or costs (15). The 5 studies of treatment patterns were conducted in the UK (2), Canada (1), the Netherlands (1), and the US (1); the 15 economic studies were conducted in the US (5), UK (3), Canada (2), Spain (2), France (1), Germany (1), and the Netherlands (1). Nine of the 16 studies were published as abstracts from professional meetings (1 reporting treatment, all 9 reporting costs). Results: Treatment patterns. Studies reporting primary data on FNHL treatment patterns tended to assess these data during the 1990s, prior to the adoption of rituximab + chemotherapy as the current standard of treatment. No more than 13 patients received rituximab in each of these studies. Of the 5 studies of treatment patterns we identified, 1 collected data through 1998, 2 through 2001, and 1 did not collect drug-specific data. One UK study reported treatment patterns through August 2003, by which date 6 patients had received rituximab. Results: Costs. The 15 cost studies identified comprised 3 cost analyses using databases (2 US, 1 UK), 2 primary studies of costs (1 US, 1 Netherlands), and 1 primary study assessing work impact (Canada). There were also 8 economic models, including 6 cost-effectiveness analyses (1 with two publications), 1 budgetary impact model, and 1 model calculating total treatment costs. Most of these 15 economic studies focus on rituximab and fludarabine. Findings suggest that the high initial cost of rituximab is offset by its low incidence of adverse events, producing equivalent average annual direct costs to those of fludarabine. Maintenance with rituximab is cost-effective versus observation alone, and the addition of rituximab to systemic chemotherapy is cost-effective versus chemotherapy alone. The single study of indirect costs (work loss) indicates highest costs among patients receiving systemic therapy. Available economic data in FNHL do not include broader societal impact of the disease. Conclusions. Although the introduction of biological therapies such as rituximab has shifted the treatment paradigm for FNHL, few studies published in the last 10 years have evaluated treatment patterns and costs of this disease. As new treatments enter the market, primary cost data and other economic information about FNHL will be needed to evaluate their relative cost-effectiveness.

First-line treatment with Bendamustine plus Rituximab for patients with indolent non-Hodgkin’s lymphoma or Mantle cell lymphoma: Real-world experience.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19540-e19540
Author(s):  
Rouslan Kotchetkov ◽  
David Susman ◽  
Lauren Gerard ◽  
Erica DiMaria ◽  
Derek Wayne Nay
Keyword(s):  
Adverse Events ◽  
Hodgkin’S Lymphoma ◽  
Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
First Line ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Mantle Cell ◽  
Grade 3

e19540 Background: Bendamustine plus rituximab (B+R) was established as a preferred first line therapy for patients with previously untreated indolent non-Hodgkin’s lymphoma based on the BRIGHT and STIL trials. However, only few reports on efficacy and safety data of this combination in the real-world setting are available to-date. Methods: We conducted a retrospective review of patients who received therapy with standard doses of B+R in our cancer center from June 2013 to January 2021. Patients with indolent non-Hodgkin’s lymphoma (iNHL) and mantle cell lymphoma (MCL) who received more than one cycle of B+R were evaluated. Results: Amongst a total of 201 patients 56% were males and 44% females. Median age at B+R initiation was 72 years (range 34-94). Follicular lymphoma (FL) (50.3%), marginal zone lymphoma (MZL) (19.4%), and lymphoplasmacytic lymphoma (LPL) (14.5%) were the most common iNHL. Stage 3 and 4 diseases represented 19.9% and 68.6% of patients. Extranodal disease was found in 35.8%. The proportion of patients with high risk disease was 48.5% for FL (FLIPI ≥3), 86.6% for LPL (WMISS score ≥2), and 80.5% for MCL (MIPI score ≥6.2). Prior history of secondary malignancy had 23.4% of patients; 11.4% patients had ECOG 3. Most common indications for B+R initiation were bulky symptomatic lymphadenopathy (69.1%), cytopenia (36.8%) and constitutional symptoms (36.8%). Fifty-eight percent of patients had more than one indication for therapy. Median number of B+R cycles delivered was 6 (range: 1-6), median dose of bendamustine was 90 mg/m2 (range 45-90). Full doses of treatment were given in 66.7% of patients, reduced in 33.3% with mean dose 78.3 mg/m2. A total of 50.8% completed 6 cycles with no delays, in 49.2% treatment was delayed (mean delay time 1.8 weeks). Overall response was 94.5%, with 77.6% complete and 16.9% partial remission. Median duration of follow-up was 35 months (range: 4-91). At the end of follow-up, event free survival (EFS) was 77.1% and overall survival (OS) was 79.6%. Six percent of patients relapsed, 8% developed secondary hematological malignancies, including 14 cases of aggressive B-cell lymphoma and 2 cases of MDS. 16.9% of patients required support with G-CSF. Grade 3-4 neutropenia was recorded in 22.4%, febrile neutropenia in 7.5%, grade 3-4 anemia in 7.9%, and grade 3-4 thrombocytopenia in 3.9% of patients. Rituximab-associated infusion reactions, skin rash, thrombophlebitis, and infection were the most common non-hematological adverse events. A total of 80.6% of patients proceeded to rituximab maintenance. Conclusions: B+R chemoimmunotherapy is feasible to administer in non-clinical trial setting. Despite more dose reduction as compared to STIL trial, B+R retained its efficacy with comparable EFS and OS. No new adverse events or increase in secondary malignancies were found.

The significance of bone marrow involvement in non-Hodgkin's lymphoma: the Eastern Cooperative Oncology Group experience.

1986 ◽  
Vol 4 (10) ◽  
pp. 1462-1469 ◽  
Author(s):  
J M Bennett ◽  
K C Cain ◽  
J H Glick ◽  
G J Johnson ◽  
E Ezdinli ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Biopsy ◽  
Hodgkin’S Lymphoma ◽  
Bone Marrow Involvement ◽  
Eastern Cooperative Oncology Group ◽  
Stage Iv ◽  
Hodgkin's Lymphoma ◽  
Stage Iii ◽  
Oncology Group ◽  
Non Hodgkin's Lymphoma

Data from four clinical trials conducted by the Eastern Cooperative Oncology Group (ECOG) were used to investigate the importance of bone marrow involvement as a prognostic factor in patients with non-Hodgkin's lymphoma (NHL). A total of 502 patients, 275 with nodular, poorly differentiated lymphocytic lymphoma (NLPD) and 227 with diffuse histiocytic lymphoma (DHL) or diffuse mixed-cell lymphoma (DML), were included in this analysis. Patients were separated into four categories: stage III, stage IV with bone marrow involvement (stage IV-M), stage IV without marrow involvement (stage IV-O), and stage IV with bone marrow and other organ involvement (stage IV-OM). Among the DHL and DML patients, the incidence of marrow involvement was 23%. However, stage IV-M patients had a prognosis that is similar to stage IV-O and stage IV-OM and worse than stage III patients. In contrast, the incidence of involvement with NLPD was 59% and patients with stage IV-M had a survival not different than stage III and not worse than stage IV-O and stage IV-OM. The results suggest that the current emphasis on bone marrow biopsy(s) as a routine diagnostic staging procedure for patients with NHL should be reevaluated. The necessity for this procedure in stage III patients with NLPD is not apparent from our data. One can still justify a bone marrow biopsy in stage I and II patients and can confirm the complete clinical response when all nodes have regressed in more advanced disease.

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