A Randomized Phase III Study of Gemcitabine, Dexamethasone, and Cisplatin Versus Dexamethasone, Cytarabine, and Cisplatin as Salvage Chemotherapy Followed by Posttransplantation Rituximab Maintenance Therapy Versus Observation for Treatment of Aggressive B-Cell and T-Cell Non-Hodgkin's Lymphoma

2005 ◽  
Vol 6 (1) ◽  
pp. 56-60 ◽  
Author(s):  
Michael Crump ◽  
Lois Shepherd ◽  
Boris Lin
Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4805-4805
Author(s):  
Sanja A. Trajkova ◽  
Lidija A. Cevreska ◽  
Irina Z. Panovska-Stavridis ◽  
Aleksandra Pivkova ◽  
Borce Georgievski ◽  
...  

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.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5356-5356
Author(s):  
Hugues de Lavallade ◽  
Reda Bouabdallah ◽  
Catherine Faucher ◽  
Sabine Furst ◽  
Jean El-Cheikh ◽  
...  

Abstract This study aimed to evaluate the role of RIC allo-SCT for relapsed or refractory non-Hodgkin’s lymphoma (NHL). We report here our experience in 25 consecutive patients transplanted in a single center for high grade (n=17) or follicular NHL (FL; n=8). In the high grade NHL group, median age was 46 (range, 24–63) years, and all 17 patients received 2 or more previous chemotherapy regimens prior to RIC allo-SCT. In addition, 12 patients (71%) had failed autologous SCT and 6 patients (35%) had chemoresistant disease at time of allo-SCT. Among the 8 patients transplanted for a heavily pretreated follicular NHL (FL), median age was 52 (range, 34–59) years and median number of prior lines of therapy was 3 (range, 2–5), with 3 patients (38%) having chemoresistant diseases and 4 patients (50%) relapsing after autologous SCT. Among the 17 patients with aggressive high grade NHL, we compared the outcome of T-cell and B-cell aggressive NHL. With a median follow-up of 15.4 (range, 3.4-65.2) months, the cumulative incidence of non-relapse mortality was 6%, (95%CI, 0.3%-31%) and the Kaplan-Meier estimate of progression-free survival (PFS) was significantly higher in the T-cell as compared to the B-cell group (P= 0.03; 100% vs. 40% at 3 years). In the FL group, the cumulative incidence of non-relapse mortality was 25% (95%CI, 3%–65%). Six patients (75%) showed objective disease response with complete remission (CR) occurring concomitantly to graft-versus-host disease, including one CR after donor lymphocytes infusion. With a median follow-up of 19 (range, 7–85) months, 6 patients from the FL group are still alive of whom 5 in CR. We conclude that a potent graft-vs.-lymphoma (GVL) may be achieved in FL patients, even those with chemoresistant disease or who have relapsed after autologous SCT. In the high grade NHL group, strategies aiming to enhance the GVL effect (Rituximab-based RIC and/or Rituximab maintenance therapy) in the B cell subtype are still needed. However, RIC allo-SCT is a feasible and promising strategy for aggressive NHL, with particularly low toxicity, and T-cell aggressive NHL benefiting most from a potent GVL effect, likely overcoming the poor prognosis usually associated with this phenotype.


2009 ◽  
Vol 13 (Suppl 2) ◽  
pp. 41-48
Author(s):  
A Boland ◽  
A Bagust ◽  
J Hockenhull ◽  
H Davis ◽  
P Chu ◽  
...  

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.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2364-2364
Author(s):  
Marjolein Pompen ◽  
P.C. Huijgens

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.


2000 ◽  
Vol 109 (3) ◽  
pp. 592-599 ◽  
Author(s):  
Tohru Inaba ◽  
Chihiro Shimazaki ◽  
Toshiya Sumikuma ◽  
Akira Okano ◽  
Mayumi Hatsuse ◽  
...  

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