Cost-effectiveness of rituximab maintenance therapy for patients with follicular lymphoma: The Spanish perspective

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8092-8092
Author(s):  
J. Gómez Codina ◽  
M. Provencio ◽  
A. Rueda ◽  
F. Capote ◽  
F. Carbonell ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Maintenance Therapy ◽  
Follicular Lymphoma ◽  
Maintenance Treatment ◽  
Progression Free Survival ◽  
Base Case ◽  
Health States ◽  
Free Survival ◽  
Rituximab Maintenance ◽  
Life Years

8092 Background: In patients with relapsed or refractory follicular lymphoma (FL) who attain a response with either cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) alone or Rituximab + CHOP, maintenance treatment with Rituximab has shown to significantly improve overall survival (OS) (85% at 3 years vs. 77%, p=0.011) and progression free survival (PFS) (51,5 vs. 14.9 months, p<0.001) as compared to observation alone (OA). We analyzed the cost-effectiveness, from a Spanish perspective, of Rituximab maintenance therapy (375mg/m2 every 3 months until progression or for 2 years) versus OA according to the population and data described for the European Organization for Research Treatment of Cancer (EORTC) 20981 study (van Oers MHJ Blood 2006). Methods: Incremental cost-effectiveness was assessed through a deterministic, three health states model (disease-free, progression and death) transition model. Base case model: PFS and OS were extrapolated from EORTC 20981 data using a Weibull distribution, Rituximab maintenance benefit was assumed to last 5 years, 10 years time horizon, 3.5% discount rate on costs and benefits, and Spanish National Health Service perspective (direct costs only). Resource use was estimated from a Spanish expert panel and EORTC 20981 study. Unit costs were obtained from local databases (May 2006 €). Health states utility values were derived from an ad hoc study. Sensitivity analyses were performed for all mentioned variables. Results: For the base case, more quality-adjusted life years (QALY), life-years (LY) and progression-free survival years per patient on maintenance therapy were obtained versus OA (incremental values of 0.85, 0.94 and 1.46, respectively). Total cost per patient was higher with Rituximab than with OA (+8,026€). Incremental cost per QALY gained was 9,358€, with a cost per LY gained of 8.493€ and a cost per PFS year gained of 5,485€. In the sensitivity analysis, values ranged between 7.263€ and 22.160€ per QALY gained. Conclusions: This study confirms that in patients with relapsed /refractory FL who attain a response with further therapy, maintenance treatment with Rituximab compared to observation alone is cost-effective. No significant financial relationships to disclose.

Maintenance Therapy with Rituximab for Follicular Lymphoma Is Cost-Effective – A Canadian Perspective.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 343-343 ◽  
Author(s):  
Bridget Maturi ◽  
Joseph R. Mikhael ◽  
William C.N. Dunlop ◽  
Dominic T. Tilden ◽  
Lisa Wong
Keyword(s):  
Maintenance Therapy ◽  
Follicular Lymphoma ◽  
Induction Therapy ◽  
Drug Acquisition ◽  
Progression Free Survival ◽  
Cost Effective ◽  
Health State ◽  
Free Survival ◽  
Rituximab Maintenance ◽  
Canadian Perspective

Abstract Background: Rituximab maintenance therapy has been shown to significantly improve overall survival (OS) (p<0.0111) and progression free survival (PFS) (p<0.0001) compared to observation alone in patients with relapsed/refractory follicular lymphoma (van Oers MHJ et al, et al. Blood. 2006 [Epub ahead of print]).The objective of this analysis was to estimate the cost-effectiveness, from a Canadian perspective, of rituximab maintenance therapy versus observation alone (OA) in relapsed/refractory follicular lymphoma patients following response to induction therapy with or without rituximab, based on data from the European Organisation for Research and Treatment of Cancer (EORTC) 20981 study (Clinical Study Report 1016350). Methods: The impact of rituximab maintenance therapy (375 mg/m2 every 3 months until progression or for 2 years) compared with OA was evaluated using a lifetime, health-state transition model. All patients entered the model following response to chemotherapy +/− rituximab as induction therapy (progression-free health state [PFHS]). The model simulates the movement of patients from PFHS to either progressed health state (PHS) or death based on the data from the study. PFS and OS following rituximab maintenance were extrapolated from 2-year Kaplan-Meier curves from the study data using a Weibull distribution. In the base case model, the PFS and OS benefits of rituximab maintenance therapy were conservatively assumed to last only 5 years. Quality of life utility values for the health states in the model were derived from a study of 165 patients using the EQ-5D questionnaire. Direct annual medical costs including drug acquisition, administration and preparation were estimated from published sources. All costs are reported in 2005 Canadian dollars (CAD). Costs and outcomes were discounted at a rate of 5%. In order to address uncertainty in point estimates, one-way sensitivity analyses were also performed. Results: From the model, the estimated life-time incremental PFS for rituximab maintenance therapy was a 1.4 year increase over OA (3.1 vs 1.7 years). OS of rituximab maintenance patients was 0.9 years longer than in OA patients (5.6 vs 4.7 years). Total cost for rituximab maintenance therapy was estimated to be CAD34,748, with the majority of costs related to drug acquisition (CAD18,652). Rituximab maintenance resulted in a gain of 0.8 Quality Adjusted Life Years (QALYs) (4.0 vs [OA] 3.2 QALYs) at an incremental cost of CAD17,136. The incremental cost effectiveness ratio (ICER) of rituximab maintenance vs OA is, therefore, estimated to be CAD20,428 per QALY gained. The ICER of rituximab maintenance was sensitive to the duration of treatment benefit and frequency of subsequent treatment. Conclusions: In patients responding to induction therapy, rituximab maintenance therapy improves overall survival and progression-free survival compared with observation alone. This pharmacoeconomic model demonstrates that maintenance therapy with rituximab is a cost-effective approach for the management of patients with follicular lymphoma.

scholarly journals Rituximab Maintenance for a Maximum of 5 Years After Single-Agent Rituximab Induction in Follicular Lymphoma: Results of the Randomized Controlled Phase III Trial SAKK 35/03

2016 ◽  
Vol 34 (5) ◽  
pp. 495-500 ◽  
Author(s):  
Christian Taverna ◽  
Giovanni Martinelli ◽  
Felicitas Hitz ◽  
Walter Mingrone ◽  
Thomas Pabst ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Follicular Lymphoma ◽  
Progression Free Survival ◽  
Short Term ◽  
End Points ◽  
Free Survival ◽  
Rituximab Maintenance ◽  
End Point ◽  
Unacceptable Toxicity

Purpose Rituximab maintenance therapy has been shown to improve progression-free survival in patients with follicular lymphoma; however, the optimal duration of maintenance treatment remains unknown. Patients and Methods Two hundred seventy patients with untreated, relapsed, stable, or chemotherapy-resistant follicular lymphoma were treated with four doses of rituximab monotherapy in weekly intervals (375 mg/m2). Patients achieving at least a partial response were randomly assigned to receive maintenance therapy with one infusion of rituximab every 2 months, either on a short-term schedule (four administrations) or a long-term schedule (maximum of 5 years or until disease progression or unacceptable toxicity). The primary end point was event-free survival (EFS). Progression-free survival, overall survival (OS), and toxicity were secondary end points. Comparisons between the two arms were performed using the log-rank test for survival end points. Results One hundred sixty-five patients were randomly assigned to the short-term (n = 82) or long-term (n = 83) maintenance arms. Because of the low event rate, the final analysis was performed after 95 events had occurred, which was before the targeted event number of 99 had been reached. At a median follow-up period of 6.4 years, the median EFS was 3.4 years (95% CI, 2.1 to 5.3) in the short-term arm and 5.3 years (95% CI, 3.5 to not available) in the long-term arm (P = .14). Patients in the long-term arm experienced more adverse effects than did those in the short-term arm, with 76% v 50% of patients with at least one adverse event (P < .001), five versus one patient with grade 3 and 4 infections, and three versus zero patients discontinuing treatment because of unacceptable toxicity, respectively. There was no difference in OS between the two groups. Conclusion Long-term rituximab maintenance therapy does not improve EFS, which was the primary end point of this trial, or OS, and was associated with increased toxicity.

scholarly journals Phase II Trial of R-CVP Followed By Rituximab Maintenance Therapy for Patients with Advanced Stage Marginal Zone Lymphoma- Consortium for Improving Survival of Lymphoma (CISL) Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1811-1811
Author(s):  
Sung Yong Oh ◽  
Won Seog Kim ◽  
Jin Seok Kim ◽  
Seok Jin Kim ◽  
Suee Lee ◽  
...  
Keyword(s):  
Informed Consent ◽  
Maintenance Therapy ◽  
Maintenance Treatment ◽  
Marginal Zone ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Marginal Zone Lymphoma ◽  
Advanced Stage ◽  
Free Survival ◽  
Rituximab Maintenance

Abstract BACKGROUND: According to our prior prospective phase II trial, Rituximab in combination with chemotherapy (R-CVP) has been shown to improve response rate (RR) and progression free survival (PFS) in patients with advanced stage marginal zone lymphoma (MZL) compared with chemotherapy alone (CVP). In spite of better RR and PFS, relapses seem to continue after immunotherapeutic treatment in these patients. Thus, eventual relapse remains an important clinical issue for the majority of patients with indolent lymphoma, and defining further ways to extend the period of remission remains an essential goal. But data from clinical trials evaluating rituximab maintenance treatment in these patients are almost limited. We aimed to evaluate the effect of maintenance treatment with rituximab on the PFS of patients with MZL. METHODS: Histologically confirmed advanced stage MZL patients who did not progress at the end of 6~8 cycles of 1st line Rituximab-CVP (cyclophosphamide 750 mg/m2 and vincristine 1.4 mg/m2 (maximum 2.0 mg), given intravenously on day 1, and oral prednisolone 100 mg on days 1-5) regimen were enrolled. Patients received 2 years of rituximab maintenance therapy (375 mg/m2 every 8 weeks). Primary objection was three year progression free survival. This trial is registered with ClinicalTrials.gov, number NCT012113095. RESULTS Between March 2010 and March 2013, a total of 47 patients were enrolled with informed consent at this trial from 17 institutes in Korea. Among these patients, 1 patient withdrew informed consent, 1 patient was screening failure with combined thyroid cancer. The median age of the evaluated 45 (32 males, 13 females) patients is 54 (range 33-77) years. Fifteen patients (33.3%) evidenced nodal MZL, 30 (66.7%) extranodal MZL (10 patients were lung, 6 ocular, and 5 stomach, in order of frequency). The IPI score were 1 in 13 (28.9%), 2 in 21 (46.7%), 3 in 9 (20%), and 4 in 2 (4.4%) patients. The patients received a total of 6 or 8 cycles of 1st line R-CVP chemotherapy were 10 (22.2%) and 35 (77.8%), respectively. There were 20 CR (44.4%), 22 PR (48.9%), and 3 SD (6.7%). Median treated number of rituximab maintenance followed by R-CVP was 12 (range 1-12). Thirty two patients (71.1%) patients completed planned 12 cycles of rituximab maintenance. Disease progression during rituximab maintenance was 8 patients, 2 patients stopped treatment because of side effects (1 abdominal pain, 1 recurrent pneumonia) 2 patients were follow-up loss. Four patients were expired (each 1 pneumonitis, pneumonia, sepsis, and disease progression). PFS and OS rate at 3 years were 78.9% and 90.6%, respectively. CONCLUSION: 2 years of rituximab maintenance therapy after R-CVP first-line chemotherapy for advanced stage MZL might be improve PFS with tolerable toxicities Disclosures Kim: Celltrion, Inc.: Consultancy, Honoraria. Lee:Amgen: Membership on an entity's Board of Directors or advisory committees.

Cost effectiveness of carfilzomib (CAR), ixazomib (IXA), elotuzumab (ELO), or daratumumab (DAR) with lenalidomide and dexamethasone (LEN+DEX) vs LEN+DEX in relapsed/refractory multiple myeloma (R/R MM).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8030-8030 ◽  
Author(s):  
Nimer Alsaid ◽  
Ali McBride ◽  
Amit Balkrishna Agarwal ◽  
Abdulaali Mutairi ◽  
Faiz Anwer ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Meta Analysis ◽  
Indirect Comparison ◽  
Progression Free Survival ◽  
Cost Utility ◽  
Sensitivity Analyses ◽  
Base Case ◽  
Health States ◽  
Chemotherapy Administration ◽  
Life Years

8030 Background: CAR, IXA, ELO, and DAR in triplet combination with LEN+DEX have shown superior efficacy over LEN+DEX in R/R MM, but their comparative efficacy and cost effectiveness has not been estimated. Methods: Network meta-analysis [NMA] and Bücher method were used to indirectly estimate comparative progression-free survival (PFS) efficacy. A 2-state Markov model (progression-free, progressed or death) was specified. Inputs included: cost of chemotherapy, administration, adverse events (AE) management, disease monitoring; utilities for health states; and disutilities for AEs. Incremental cost effectiveness (ICER) and cost utility ratios (ICUR) were calculated for resp. PFS life years (PFS LY) and quality adjusted life years (PFS QALY) gained in base case and probabilistic sensitivity analyses (PSA). Results: NMA and Bücher indirect comparison methods yielded similar PFS hazard ratios (HR), revealing superiority of DAR+LEN+DEX over other triplets in terms of PFS (Table). Using the exponential distribution to fit PFS data, our cost effectiveness analysis indicated that all 4 triplet regimens were associated with additional PFS LY and QALY gained over LEN+DEX at additional cost. DAR+LEN+DEX was associated with the greatest PFS LY and QALY gained at the lowest relative cost, yielding superior ICER and ICUR estimates compared to other triplet regimens. Conclusions: The superior PFS efficacy of DAR+LEN+DEX is associated with positive cost effectiveness and cost utility in the setting of R/R MM. [Table: see text]

The MAXIMA Study: Safety of Rituximab (MabThera®) Maintenance Therapy in Patients with Follicular Non-Hodgkin’s Lymphoma Who Have Responded to Induction Therapy.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4475-4475 ◽  
Author(s):  
Michael K. Wenger ◽  
Robin Foa ◽  
Luca Arcaini ◽  
Andrej Vranovský ◽  
Valentina Ivanova ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Follicular Lymphoma ◽  
Induction Therapy ◽  
Survival Benefit ◽  
Progression Free Survival ◽  
Rapid Infusion ◽  
Free Survival ◽  
True Incidence ◽  
Rituximab Maintenance ◽  
Wide Range

Abstract Five randomised trials have reported that rituximab maintenance therapy leads to a progression free survival advantage in indolent NHL, with the largest trial (EORTC 20981) showing a progression-free survival benefit of 3 years in patients with follicular lymphoma compared to observation, and a significant overall survival benefit approximately halving the hazard of death. The primary objective of the current study, which involves 23 countries, initiated in August 2006, and aiming to recruit approximately 500 patients, is to extend the safety database for rituximab maintenance within a less stringent setting, allowing for a wide range of induction therapies. The study also examines the ‘real life’ safety associated with rapid-infusion of rituximab. The sample size has been calculated to detect at least one rare event with a true incidence of 0.32% with 80% power. Patients with first line or relapsed/refractory follicular lymphoma achieving a response after rituximab containing induction therapy are eligible to receive rituximab at the standard dose of 375 mg/m2 every eight weeks for 2 years. One-hundred-and-thirty-nine patients have been enrolled to date for whom demographic data is available: Median age of the patient population is 56 years [range: 29 to 82]. Forty-eight percent of the patients are male. Fifty-nine percent of the patients have no relevant medical history except for NHL. Among those who do, cardiovascular diseases is the most common. Most patients (∼ 74%) have a pre-induction FLIPI score of 2 or less. Thirty-five and 49% of the patients, respectively, have grade 1 or 2 follicular NHL. Most patients (75%) have received one line of treatment (including present study induction) since diagnosis, but some patients have received up to 4 previous lines of treatment. Sixty-two percent of the patients received an anthracycline-based regimen in combination with rituximab as induction therapy, whilst 25% and 9% respectively received an alkylating-based or purine analogue-based regimen. Ninety-four patients have received at least one infusion of rituximab as maintenance therapy, less than 40% of these patients having received two or more infusions to date. In total, 162 infusions of rituximab have been administered, 25% (40/162) of these having been administered as rapid infusion. Twenty events unrelated to study medication have been reported in 9 patients, with most of these events (19/20) being CTC grade 1 or 2. There was one patient who experienced a CTC grade 1 infusion related adverse event (erythema) which was not associated with rapid infusion. At the time of the report, there were no SAEs in the clinical database, but 4 SAEs had been reported to Roche, including 1 death resulting from pre-existing cardiac arrhythmia and not related to rituximab. Based on this initial sample, there does not appear to be any safety issue associated with 2-monthly rituximab maintenance therapy, whether administered as rapid infusion or not.

Rituximab maintenance for the Treatment of patients with Follicular Lymphoma: Systematic Review and Meta-Analysis of Randomized Trials - 2010 Update.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1798-1798 ◽  
Author(s):  
Liat Vidal ◽  
Anat Gafter-Gvili ◽  
Gilles Salles ◽  
Martin H. Dreyling ◽  
Michele Ghielmini ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Follicular Lymphoma ◽  
Survival Benefit ◽  
Maintenance Treatment ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Free Survival ◽  
Rituximab Maintenance

Abstract Abstract 1798 Rituximab maintenance for the treatment of patients with follicular lymphoma: systematic review and meta-analysis of randomized trials - 2010 update. Liat Vidal, Anat Gafter-Gvili, Gilles Salles, Martin Dreyling, Michele Ghielmini, Shu-Fang Hsu Schmitz, Ruth Pettengell, Mathias Witsenz-Harig, Ofer Shpilberg. Follicular lymphoma (FL) is characterized by slow growth and an initially high rate of response to treatment, but patients typically relapse and experience progressive disease. Rituximab in combination with chemotherapy has been shown to improve overall survival (OS) in patients with FL compared with chemotherapy alone. In order to evaluate the effect of maintenance treatment with rituximab on the OS of patients with FL we performed a systematic review and meta-analysis in 2007. Updated results from these studies and new clinical trials are reported here. Methods: A systematic review and meta-analysis of randomized controlled trials that compared rituximab maintenance therapy with observation or treatment at relapse (no maintenance therapy). In June 2010 we updated our 2007 search in The Cochrane Library, MEDLINE, LILACS, conference proceedings, and databases of ongoing trials. Two reviewers independently assessed the quality of the trials and extracted data. HRs for time-to-event data were estimated and pooled. Results: The search in 2007 identified five eligible trials including 1143 adult patients. The results of the meta-analysis of 985 patients with FL were previously reported. The present search identified six additional included trials; three of them had no current available outcome data. Three of the trials that were included in our first report had long term outcomes that were available for the current meta-analysis. Patients treated with maintenance rituximab had statistically significant better OS compared to patients in the observation arm or patients treated at relapse (HR for death 0.75, 95% confidence interval (CI) 0.61 to 0.91, 2283 patients, Figure). Patients with refractory or relapsed (i.e., previously treated) FL had a significant survival benefit with maintenance rituximab therapy (HR for death 0.72, 95% CI 0.57 to 0.91, 909 patients), whereas previously untreated patients did not (HR for death 0.83, 95% CI 0.56 to 1.23, 1374 patients). Progression free survival was improved in each of the included trials, pooled HR 0.54 95% CI 0.48 to 0.61, n=2283. This effect was consistent both in patients who received rituximab maintenance after their first induction therapy (HR 0.53, 95% CI 0.44 to 0.63, n=1374), and in those who received maintenance rituximab after two or more inductions (HR 0.63, 95% CI 0.50 to 0.79, n=804), and following different induction therapies: rituximab alone (HR 0.54, 95% CI 0.40 to 0.73, n=240), chemotherapy alone (HR 0.49, 95% CI 0.37 to 0.66, n=308), and rituximab-chemotherapy (HR 0.58, 95% CI 0.48 to 0.70, n=1352). The rate of infection-related adverse events was higher with rituximab maintenance treatment (Risk ratio (RR) 1.99, 95% CI 1.21 to 3.27). The rate of grade 3/4 adverse events was higher with rituximab maintenance (RR 1.47 95% CI 1.19 to 1.83). Conclusions: Rituximab maintenance improves OS and disease control in patients with FL after a successful induction therapy. The accumulating data from new and updated clinical trials did not change the results of our former meta-analysis. While a clear survival benefit is shown only for patients with relapsed or refractory FL, progression free survival is improved after first induction as well as after two or more inductions. Disclosures: Salles: Roche: Honoraria. Dreyling:Roche: . Ghielmini:Roche: Consultancy. Pettengell:Roche: Consultancy, Honoraria. Shpilberg:Roche: Consultancy.

Maintenance Therapy for Patients with Mantle Cell Lymphoma (MCL) - a Systematic Review and Meta-Analysis of Randomized Controlled Trials (RCTs)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1802-1802 ◽  
Author(s):  
Liat Vidal ◽  
Anat Gafter-Gvili ◽  
Martin H. Dreyling ◽  
Michael Unterhalt ◽  
Pia Raanani ◽  
...  
Keyword(s):  
Systematic Review ◽  
Maintenance Therapy ◽  
Follicular Lymphoma ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Interferon Alfa ◽  
Event Free Survival ◽  
First Line ◽  
Free Survival ◽  
Rituximab Maintenance

Abstract Background: MCL is characterized by a dismal long term prognosis with a median overall survival of 3-5 years. Rituximab maintenance treatment (MR) improves survival of patients with follicular lymphoma, and its effect was assessed for MCL patients in several trials with inconsistent results. Other agents as bortezomib were also evaluated as maintenance therapy for MCL. Aims: We performed a systematic review and meta-analysis of RCTs in order to assess the effect of maintenance therapy on clinical outcomes of patients with MCL. Methods: We included RCTs that compared any type of maintenance to no maintenance or a different maintenance for patients with MCL, either in first line or relapsed disease. In July 2016 we searched The CochraneLibrary, MEDLINE, conference proceedings, and databases of ongoing trials. Two reviewers independently assessed the qualityof the trials and extracted data. The primary outcome wasall cause mortality. Secondary outcomes included progression free survival (PFS) and infectious adverse events. Relative risk (RR) for dichotomous data and hazard ratio (HR) for time to event datawere estimated and pooled using random-effects model. Results We identified 6 trials that reported relevant outcomes, conducted between the years 1998 to 2012 and randomizing 857 patients with MCL. Most patients were males, with a median age ranging from 57 to 70 years, and predominantly good performance status. Ninety-six percent of the patients received their first line of treatment. MIPI score was reported in three trials: 20 to 42 percent of patients had a high MIPI score. Induction therapy included rituximab in all trials. In five trials chemotherapy induction was applied and consisted of fludarabine, cyclophosphamide (FC) and mitoxantrone (Forstpointner, Blood 2006), cyclophosphamide, vincristine, adriamycin, prednisone (CHOP) or FC in one trial (Kluin-Nelemans et al.), bendamustine (Rummel et al.), DHAP followed by autologous stem cell transplantation (ASCT) (Le Gouill et al.), and CHOP/cytarabine followed by ASCT (Doorduijn et al.); in one trial rituximab was given alone (Ghielmini et al.). Maintenance consisted of rituximab in five trials and bortezomib in one trial (Doorduijn et al.). The control group received no maintenance in two trials and interferon alfa in one trial. All included trials were judged at low risk of selection bias, none were blinded. No statistically significant effect on mortality rate was shown with rituximab maintenance therapy compared to no maintenance or interferon alfa RR 0.72, 95% CI 0.50 to 1.04, I2 of heterogeneity 57%, 751 patients. The RR of mortality with bortezomib maintenance was 0.67, 95% CI 0.12 to 3.71, but that is based on only 60 patients. PFS improved with rituximab maintenance compared to no maintenance or interferon alfa: HR 0.59, 95% CI 0.46 to 0.75. With bortezomib maintenance vs. no maintenance the HR of event free survival was 0.84, 95% CI 0.32 to 2.20. There was no statistically significant difference in infection rate with or without maintenance (RR 0.80, 95% CI 0.37 to 1.69, 419 patients). Conclusions Maintenance therapy improved PFS of patients with MCL, but no survival benefit could be shown. The pooled analysis is based mainly on the results of rituximab maintenance as data of the effect of bortezomib maintenance is scarce. The absence of significant increase of infection rate as opposed to maintenance rituximab in follicular lymphoma might be attributed to the small sample size. Based on these results patients treated for both first line and relapsed/refractory MCL should receive rituximab maintenance after achieving response to induction. Table disease control (*progression free survival, **event free survival) of patients with MCL who responded to induction and treated with rituximab maintenance compared to observation or interferon alfa. Table. disease control (*progression free survival, **event free survival) of patients with MCL who responded to induction and treated with rituximab maintenance compared to observation or interferon alfa. Disclosures Dreyling: Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Clinical outcome of patients with follicular lymphoma receiving chemoimmunotherapy in the PRIMA study is not affected by FCGR3A and FCGR2A polymorphisms

Blood ◽  
2012 ◽  
Vol 120 (13) ◽  
pp. 2650-2657 ◽  
Author(s):  
Hervé Ghesquières ◽  
Guillaume Cartron ◽  
John Francis Seymour ◽  
Marie-Hélène Delfau-Larue ◽  
Fritz Offner ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Follicular Lymphoma ◽  
Response Rate ◽  
Single Agent ◽  
Progression Free Survival ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Free Survival ◽  
Rituximab Maintenance

Abstract In patients with follicular lymphoma treated with single-agent rituximab, single nucleotide polymorphisms in the FCGR3A gene are known to influence response and progression-free survival. The prognostic role of FCGR3A and FCGR2A polymorphisms in patients with follicular lymphoma treated with rituximab and chemotherapy combination remains controversial and has not been evaluated in the context of rituximab maintenance. FCGR3A and FCGR2A single nucleotide polymorphisms were evaluated in, respectively, 460 and 455 patients treated in the PRIMA study to investigate whether these were associated with response rate and patient outcome after rituximab chemotherapy induction and 2-year rituximab maintenance. In this representative patient cohort, complete and unconfirmed complete responses after rituximab chemotherapy were observed in 65%, 67%, 66% (P = .86) and 60%, 72%, 66% (P = .21) of FCGR3A VV, VF, FF and FCGR2A HH, HR, RR carriers, respectively. After 2 years of rituximab maintenance (or observation), response rates did not differ among the different genotypes. Progression-free survival measured from either treatment initiation or randomization to observation or maintenance was not influenced by these polymorphisms. These data indicate that FCGR3A and FCGR2A polymorphisms do not influence response rate and outcome when rituximab is combined with chemotherapy or used as maintenance treatment. The PRIMA study is registered at www.clinicaltrials.gov as NCT00140582.

Oligometastasiertes nicht kleinzelliges Lungenkarzinom: Vorteile einer lokalen Konsolidierungstherapie nutzen

2019 ◽  
Vol 7 (6) ◽  
pp. 312-313
Author(s):  
Wolfgang Schütte ◽  
Miriam Möller
Keyword(s):  
Adverse Events ◽  
Maintenance Therapy ◽  
Systemic Therapy ◽  
Maintenance Treatment ◽  
Therapy Group ◽  
Progression Free Survival ◽  
Cancer Center ◽  
First Line ◽  
Free Survival ◽  
Md Anderson

Background: Evidence from retrospective studies suggests that disease progression after first-line chemotherapy for metastatic non-small-cell lung cancer (NSCLC) occurs most often at sites of disease known to exist at baseline. However, the potential effect of aggressive local consolidative therapy for patients with oligometastatic NSCLC is unknown. We aimed to assess the effect of local consolidative therapy on progression-free survival. Methods: In this multicentre, randomised, controlled, phase 2 study, eligible patients from three hospitals had histological confirmation of stage IV NSCLC, three or fewer metastatic disease lesions after first-line systemic therapy, an Eastern Cooperative Oncology Group performance status score of 2 or less, had received standard first-line systemic therapy, and had no disease progression before randomisation. First-line therapy was four or more cycles of platinum doublet therapy or 3 or more months of EGFR or ALK inhibitors for patients with EGFR mutations or ALK rearrangements, respectively. Patients were randomly assigned (1:1) to either local consolidative therapy ([chemo]radiotherapy or resection of all lesions) with or without subsequent maintenance treatment or to maintenance treatment alone, which could be observation only. Maintenance treatment was recommended based on a list of approved regimens, and observation was defined as close surveillance without cytotoxic treatment. Randomisation was not masked and was balanced dynamically on five factors: number of metastases, response to initial therapy, CNS metastases, intrathoracic nodal status, and EGFR and ALK status. The primary endpoint was progression-free survival analysed in all patients who were treated and had at least one post-baseline imaging assessment. The study is ongoing but not recruiting participants. This study is registered with ClinicalTrials.gov, number NCT01725165. Findings: Between Nov 28, 2012, and Jan 19, 2016, 74 patients were enrolled either during or at the completion of first-line systemic therapy. The study was terminated early after randomisation of 49 patients (25 in the local consolidative therapy group and 24 in the maintenance treatment group) as part of the annual analyses done by the Data Safety Monitoring Committee of all randomised trials at MD Anderson Cancer Center, and before a planned interim analysis of 44 events. At a median follow-up time for all randomised patients of 12·39 months (IQR 5·52-20·30), the median progression-free survival in the local consolidative therapy group was 11·9 months (90% CI 5·7-20·9) versus 3·9 months (2·3-6·6) in the maintenance treatment group (hazard ratio 0·35 [90% CI 0·18-0·66], log-rank p=0·0054). Adverse events were similar between groups, with no grade 4 adverse events or deaths due to treatment. Grade 3 adverse events in the maintenance therapy group were fatigue (n=1) and anaemia (n=1) and in the local consolidative therapy group were oesophagitis (n=2), anaemia (n=1), pneumothorax (n=1), and abdominal pain (n=1, unlikely related). Interpretation: Local consolidative therapy with or without maintenance therapy for patients with three or fewer metastases from NSCLC that did not progress after initial systemic therapy improved progression-free survival compared with maintenance therapy alone. These findings suggest that aggressive local therapy should be further explored in phase 3 trials as a standard treatment option in this clinical scenario. Funding: MD Anderson Lung Cancer Priority Fund, MD Anderson Cancer Center Moon Shot Initiative, and Cancer Center Support (Core), National Cancer Institute, National Institutes of Health.

Comparing The Cost-Effectiveness Of Rituximab Maintenance (MR) and Radioimmunotherapy (RIT) Consolidation Therapy Following First-Line Chemo/Immunochemotherapies For Follicular Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2923-2923
Author(s):  
Qiushi Chen ◽  
Turgay Ayer ◽  
Adam C Rose ◽  
Loretta J. Nastoupil ◽  
Christopher R. Flowers
Keyword(s):  
Cost Effectiveness ◽  
Adverse Events ◽  
Follicular Lymphoma ◽  
Progression Free Survival ◽  
Consolidation Therapy ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Frontline Treatment ◽  
The Cost

Abstract Background Follicular lymphoma (FL), the most common indolent non-Hodgkin's lymphoma, has been regarded incurable and no consensus in management strategy has existed so far. In current clinical practice, the most commonly used frontline therapy is the immunochemotherapy (R-chemotherapy). Several phase III randomized trials - ECOG1496(Hochster, JCO2009), PRIMA(Salles, Lancet2011), and FIT(Morschhauser, JCO2008) - have shown that rituximab maintenance (MR) therapy and radioimmunotherapy (RIT) consolidation in addition to the frontline R-chemotherapy can improve progression-free survival (PFS) and help achieve a higher response quality. We conducted a cost-effectiveness analysis of maintenance or consolidation therapy versus observation after frontline treatment from the US payer's perspective. Methods We developed separate Markov models over patients' lifetime for PRIMA, ECOG, and FIT trial to compare the cost and effectiveness of observation with MR/RIT after completion of frontline treatment. Published progression free survival (PFS) and overall survival (OS) curves were extracted and fitted with Log-logistic regression survival model. Progression risks and cause-specific mortality after first-line treatment were extrapolated from the corresponding fitted PFS and OS model for each arm. Risk estimates after second-line treatment were identical for different models, estimated from the published survivals of observation arm in EORTC20981 trial. Costs for administration, monitoring, and management of adverse events were based on Medicare reimbursement rates for physician services, and drug costs were the wholesale acquisition cost, all valued in 2013 US dollars. In the microsimulation, initial age at diagnosis was sampled from the age distribution according to Surveillance Epidemiology and End Result (SEER) database. All costs and effectiveness were discounted at 3% per year. Primary outcomes were incremental cost per life-year gained (LY) and cost per quality adjusted life-year (QALY) gained. Model robustness in parameter uncertainties were addressed by one-way and probabilistic sensitivity analysis. Results Compared with observation, MR therapy provided 0.998 QALYs (0.901 LYs) at a cost of $43234 in PRIMA study, 1.070 QALYs (0.866 LYs) at a cost of $50146 in ECOG study, while RIT consolidation provided 0.795 QALYs (0.653 LYs) at a cost of $46085 in FIT trial. The incremental cost per QALY gained for RIT in FIT, and MR in PRIMA and ECOG were $57975, $43301, and $46844, respectively. From the table summarizing effectiveness and cost results, RIT and MR had comparable incremental QALYs before first progression, while RIT had higher incremental costs of adverse events due to relatively high incidence of adverse events in the RIT arm. Conclusions We used the same modeling framework and consistent parameter estimates to evaluate the cost-effectiveness of MR and RIT compared to observation after frontline treatment for FL patients. All strategies showed favorable cost-effectiveness profile with ICER below $100,000/QALY willingness-to-pay. Differences in induction therapies in three trials should also be noted when the ICERs of three models are compared. Disclosures: Flowers: Abbott, Celgene, Millennium/Takeda, Sanofi, Spectrum, Janssen: Research Funding; Celgene, Genentech Bio-oncology : Consultancy.

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