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.

Cost-effectiveness of rituximab plus CVP for first-line treatment of advanced indolent lymphoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6583-6583
Author(s):  
J. Hornberger ◽  
C. Reyes ◽  
E. Verhulst ◽  
D. Lubeck ◽  
N. Valente
Keyword(s):  
Overall Survival ◽  
Cost Effectiveness ◽  
Follicular Lymphoma ◽  
Cost Effective ◽  
Sensitivity Analyses ◽  
Line Treatment ◽  
First Line ◽  
Economic Implications ◽  
The Cost ◽  
First Line Treatment

6583 Background: The addition of rituximab (RTX) to CVP (cyclophosphamide, vincristine, prednisone) in the treatment of advanced follicular lymphoma increases median time to progression by 17 months (15 month v 32 months; p < 0.0001) (Marcus et al, Blood 2005). A societal cost-effectiveness analysis was performed to estimate projected lifetime clinical and economic implications of this treatment. Methods: The cost-effectiveness (CE) of RTX + CVP versus CVP was estimated for a 50 yr old patient. Kaplan-Meier estimates of progression-free and overall survival, up to 4 years, were obtained from the M39021 trial. After 4 years, transition rates from initiation of treatment to progression or death were assumed to be the same in both arms. The clinical and economic implications of relapse and its treatment were included in the model. Incremental costs associated with addition of RTX were estimated using Medicare reimbursement rates and published retail price data. Costs included drug and administration costs, adverse events, treatment of relapses, and end-of-life costs. Utility estimates were derived from the literature and a 3% discount rate was employed. Results: Projected mean overall survival is 1.5 yrs longer for patients assigned to RTX+ CVP versus only CVP (13.7 v 12.2 yrs). The addition of RTX to CVP is estimated to cost an additional $26,439 on average, with an expected gain of 0.85 year of quality-adjusted survival. Over a lifetime, the cost per QALY gained is $31,329. Sensitivity analyses revealed that the variables that most influenced cost-effectiveness were the time horizon (range: $18,800- $31,240) and the unit drug cost of RTX (range: $24,000-$38,000). Conclusion: The model estimates a cost-to-QALY gained ratio that is below that of many treatments used for oncology patients. The use of RTX + CVP for first-line treatment of advanced follicular lymphoma is projected to be cost-effective compared to CVP alone under a range of sensitivity analyses. No significant financial relationships to disclose.

The societal impact of obinutuzumab in the first-line treatment of patients with follicular lymphoma in Germany

2020 ◽  
Vol 9 (14) ◽  
pp. 1017-1026
Author(s):  
Sarah Hofmann ◽  
Sebastian Himmler ◽  
Dennis Ostwald ◽  
Ulrich Dünzinger ◽  
Aino Launonen ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Value Added ◽  
Progression Free Survival ◽  
Unpaid Work ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Productivity Measure ◽  
Productivity Gains ◽  
First Line Treatment

In this study, we assessed the productivity gains associated with the use of obinutuzumab in combination with chemoimmunotherapy (G-chemo) in first-line treatment among follicular lymphoma patients. Health benefits, measured as an increase in progression-free survival, were translated into productivity gains in both paid and unpaid work using gross value added as productivity measure. From 2017 to 2030, 11,870 overall progression-free years can be gained by utilizing obinutuzumab. These progression-free years correspond to undiscounted productivity gains of about €187.9 million in paid work and about €535.9 million in unpaid work. Our study shows that the benefits of the use of obinutuzumab in the first-line treatment of follicular lymphoma extend beyond clinical advantages.

Addition of bevacizumab to first-line FOLFOX4 and overall survival in patients with metastatic colorectal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 610-610 ◽  
Author(s):  
Mitsukuni Suenaga ◽  
Satoshi Matsusaka ◽  
Nobuyuki Mizunuma ◽  
Eiji Shinozaki ◽  
Mariko Ogura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Median Overall Survival ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

610 Background: In our previous report, addition of bevacizumab (BV) to the FOLFOX4 regimen appeared to significantly improve response rate, progression-free survival and overall survival in first-line treatment for patients with metastatic colorectal cancer (mCRC) (Suenaga M, et al. ASCO-GI 2011 [abstr 588]). Update results met median overall survival, and statistical analysis of survival was performed. Methods: An observational cohort study was carried out on all eligible patients scheduled to receive FOLFOX4 (n = 128) or FOLFOX4+BV (n = 85) between 2005 and 2007, 2007 and 2009, with a median follow-up time of 20.4 months vs. 30.2 months, respectively. Predefined efficacy endpoints were treatment characteristics, response rates, progression-free survival, and overall survival in the periods of time observed. Results: Median progression-free survival was 9.9 months (95% CI, 8.4-11.4) in the FOLFOX4- and 17 months (95% CI, 11.8-22.3) in the FOLFOX4+BV-treated patients (p=0.002). Median overall survival times were 20.5 months (95% CI, 16.9-24) and 38.8 months (95% CI, 32.9-44.8) in the two groups, respectively (p<0.001). In the ECOG PS 0 population, progression-free survival in the FOLFOX4 and FOLFOX4+BV groups was 11 months and 17 months with a hazard ratio of 0.63 (95% CI, 0.44-0.89) in favour of FOLFOX4+BV, similarly in OS with a hazard ratio of 0.53 (95% CI, 0.36-0.77). Subgroup population received 5-FU plus leucovorin (FL) as maintenance during oxaliplatin discontinuation due to adverse events had longer PFS or OS in both groups, though no significance. PFS were 14.7 and 21.6 months, and OS were 29 and 45.9 months, respectively. Secondary resection was performed more in FOLFOX4+BV (11.8%) than FOLFOX4 (3.9%) patients. Conclusions: These data indicate potential survival benefits from the addition of BV to the FOLFOX4 regimen as first-line treatment for mCRC. Maintenance using FL after discontinuation of oxaliplatin due to adverse events appeared to be an essential factor for better survival.

Galician lung cancer group: Afatinib´s data as first-line treatment for elderly patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20662-e20662
Author(s):  
Sara Agraso Busto ◽  
Vanesa Varela ◽  
Natalia Fernández Núñez ◽  
Jose-luis Firvida ◽  
Lucía Santomé ◽  
...  
Keyword(s):  
Adverse Events ◽  
Elderly Patients ◽  
Progression Free Survival ◽  
Skin Toxicity ◽  
Treatment Interruption ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Cancer Group ◽  
First Line Treatment

e20662 Background: There are scarcy data or studies on safety and efficacy of afatinib in elderly patients. Methods: Retrospective study on patients from differents hospitals in Galicia (Spain) diagnosed of metastasic lung adenocarcinoma with EGFR positive mutation who have received first line treatment with afatinib between July 2015 and September 2018 were included. Main objectives were to asses safety, dose reductions and as well as its effects on effectiveness of the treatment in patients 70 years old or older (elderly patients) comparing with data from patients under 70 years of age. Results: 45 patients were included in our analysis (33 women, 12 men). Median age was 71.2 years (39-91) with 24 patients (53.3%) being 70 years old or older. Common adverse events grade 3/4 were mucositis and skin toxicity (28.6% in patients under 70 years and 20.8% in elderly patients) and diarrhea (9.5% and 16.7% respectively). The dose was reduced in 47.6% patients under 70 vs 75% in elderly patients. Treatment was discontinued in 14.3% patients vs 20.8% patients respectively owing to adverse events. Overall response was 76% and 62.5% respectively. Disease control rates were 90.3% (95% CI: 96.7-83.8) and 83.3% (95% CI: 98.2-68.4) respectively. Median progression free survival (PFS) was 27 months (95% CI 14.8-39.1) and overall survival was not reached. By ages, median PFS was 20 months (95% CI: 7.4-32.5) vs not reached in elderly patients although being unable to demonstrate differences in progression-free survival between both groups. Conclusions: PFS was 20 months in people under 70 years vs not reached in elderly patients. Elderly patients need more treatment interruption or dose adjustments compared with younger patients, but this does not seem to impair safety and does not compromise effectiveness either.

Management of Grade 3B Follicular Lymphoma (FL) Outside Clinical Trials: A Multicentric Retrospective Analysis on Behalf of Fondazione Italiana Linfomi (FIL)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2716-2716
Author(s):  
Barbara Botto ◽  
Federica Cavallo ◽  
Manuela Zanni ◽  
Antonella Anastasia ◽  
Chiara Rusconi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Follicular Lymphoma ◽  
Retrospective Analysis ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Rituximab Maintenance ◽  
First Line Treatment

Abstract Introduction: Follicular lymphoma grade 3 is recognized as a distinct entity in the World Health Organization classification of lymphoma. It is further classified into grade 3a and 3b depending on percentage of centroblasts. There is no consensus about its clinical course because some studies indicate an indolent behavior but others describe a more aggressive. Large systematic studies are missing in particular for 3b follicular lymphoma which is often considered as a separate entity. Methods: We performed a retrospective multicentric study on a group of 3b FL patients diagnosed in nine Italian FIL centers between November 2002 and January 2015. Planned inclusion criteria at enrollment were first line Rituximab containing regimen treatment and diagnostic samples availability for central pathologic review. Aim of the study was to determine clinical response, OS and PFS. Tumor response was based on the International Working Group response criteria. Survival analysis was performed with Kaplan-Meier method. Results: We enrolled a total of 51 patients, 50 evaluable for response at the time of analysis; median age was 62 yrs (range 48-71), 29 (56%) in stage III-IV, 10 (20%) with B symptoms. First line treatment was R-CHOP in the majority of patients 47 (92%), R-Bendamustine and R-CVP in 2 (4%) respectively. Seven patients (14%) received Rituximab maintenance after first line, six (12%) underwent high dose chemotherapy and autologous stem cell transplant (ASCT) as consolidation therapy and 5 (10%) were treated with local radiotherapy on residual disease. We observed CR in 48 patients (96%), PR in 1 (2%), PD in 1(2%). Ten patients relapsed or progressed after first line treatment and four of them died, three for progressive disease and one due to senile dementia while in CR. No relapses were recorded in pts receiving Rituximab maintenance but the advantage was not statistically significant and the number of patients receiving maintenance was low. With a median follow up of 63 months from diagnosis (IQR 33-82), 3-yrs PFS and OS rates were 82% and 93% (fig 1 and 2) with the evidence of a plateau in both survival curves after 5 years observation. Central pathologic review is ongoing. Conclusion: With the limit of a retrospective analysis our study confirms the clinical benefit of a combined modality treatment with Rituximab plus antracycline-containing chemotherapy in patients with 3b FL. Our results compare favorably with those previously reported in studies without Rituximab, that failed to show a plateau with 3-yrs PFS ranging between 22% and 52%. This results need to be confirmed with a longer follow up and after the planned pathologic review. Figure 1. Progression-Free Survival. Median Follow-up 62 months (IQR 33-82). Figure 1. Progression-Free Survival. Median Follow-up 62 months (IQR 33-82). Figure 2. Overall Survival. Median Follow-up 63 months. Figure 2. Overall Survival. Median Follow-up 63 months. Disclosures No relevant conflicts of interest to declare.

The cost-effectiveness of new first-line therapies approved in advanced hepatocellular carcinoma

2021 ◽  
pp. 107815522110450
Author(s):  
Jacopo Giuliani ◽  
Beatrice Mantoan ◽  
Andrea Bonetti
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cost Effectiveness ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Control Groups ◽  
First Line ◽  
Free Survival ◽  
The Difference ◽  
The Cost

The introduction of targeted agents (lenvatinib) and immune-based therapies (atezolizumab in combination with bevacizumab) for first-line advanced hepatocellular carcinoma provided new therapeutic options. The aim of this paper was to assess the cost-effectiveness of lenvatinib and the combination of atezolizumab plus bevacizumab in first-line for advanced hepatocellular carcinoma. Pivotal phase III randomized controlled trials were considered. Incremental cost-effectiveness ratio was calculated as the ratio between the difference of the costs in the intervention and in the control groups (pharmacy costs) and the difference between the effect in the intervention and in the control groups (progression free survival). One thousand four hundred and fifty five patients were included. The lowest cost for month of progression free survival-gain was associated with lenvatinib, with 139.24 € per month progression free survival-gained. Combining pharmacological costs of drugs with the measure of efficacy represented by progression free survival, lenvatinib is a cost-effective treatment in first-line for advanced hepatocellular carcinoma.

COMPARATIVE PHARMACOECONOMIC EVALUATION OF THE USE OF AFATINIB AND GEFITINIB IN THERAPY FOR LUNG CANCER

2017 ◽  
Vol 63 (1) ◽  
pp. 38-51
Author(s):  
Denis Fedyaev ◽  
V. Ignateva ◽  
Yelena Derkach ◽  
Sergey Zyryanov ◽  
Konstantin Laktionov ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Egfr Mutation ◽  
Progression Free Survival ◽  
Baseline Scenario ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy ◽  
Activating Egfr Mutation ◽  
The Cost

Background: Preliminary results of the study of clinical effectiveness and safety of afatinib in comparison with gefitinib as the first line therapy for the patients with the metastatic non-small-cell lung cancer (NSCLC) and activating EGFR mutation have been reported in December of 2015. According to this study afatinib has significantly increased the rate of progression-free survival (PFS) (RR = 0.73; 95% CI, 0.57, 0.95; р = 0.0165), as well as the time before treatment discontinuation (TTD) (RR = 0.73; 95% CI, 0.58, 0.92; р = 0.0073) in comparison with gefitinib and the objective response rate (ORR) (70% vs 56%, р = 0.0083). The aim of the present study: Economic evaluation of afatinib in comparison with gefitinib as the first line therapy during the long-term treatment of locally advanced or metastatic NSCLC in the patients with the activating EGFR mutation. Methods: The cost-effectiveness analysis has been performed using Markov model. The model has been constructed on the basis of the results of clinical study LUX-Lung 7, taking into account the results of the study LUX-Lung 3. The direct medical costs have been taken into account: the cost of drug treatment of metastatic NSCLC during the first and second line therapy, the expenses for palliative care, correction of adverse events, as well as for the follow-up of patients in the course of the treatment. The cost/effectiveness ratio (CER) (Rubles/ Quality adjusted life year, or QALY) has been calculated for afatinib and gefitinib. In the baseline scenario (all patients with frequent activating mutations) the cost-effectiveness of afatinib for all patients with activating EGFR mutation has been evaluated; in addition the costs and outcomes in patients with Del19 and L858R mutation have been analyzed separately. The probabilistic sensitivity analysis of the analysis results to the variability of initial parameters has been performed. Results: In the baseline scenario the cost of first year treatment with afatinib as the first line therapy has been by 13.56% cheaper than the cost of treatment with gefitinib and amounted to 1.058 million Rubles for afatinib and 1.224 million Rubles for gefitinib. The general expenses for the first year of treatment have amounted to 946 726 Rubles for afatinib, and 1 024 096 Rubles for gefitinib. In the baseline scenario the modeled progression-free survival for afatinib has amounted to 13.15 months and for gefitinib to 10.65 months. The total direct medical costs for first 3 years of treatment for afatinib have amounted to 1.577 million Rubles, for gefitinib 1.585 million Rubles, the number of QALY gained - 1.341 and 1.280 correspondingly. CER for afatinib has amounted to 1.176 million, for gefitinib - 1.239 million Rubles/QALY In the additional scenarios the same results have been demonstrated: CER for afatinib was less than for gefitinib. Conclusions: The administration of afatinib leads to the better clinical results, expressed by the increase of the rate of progression-free survival and longer-term therapy on retention of life quality of the patients in comparison with the administration of gefitinib accompanying by the cost advantage. Subsequently the cost - effectiveness ratio for afatinib is better than for gefitinib. Afatinib is the dominant alternative for the treatment of NSCLC during first line therapy in comparison with gefitinib. The prescription of afatinib offers the possibility to spare funds in the health system and is appropriate from pharmacoeconomic standpoint.

Cost-effectiveness analysis of osimertinib for first-line treatment of locally advanced or metastatic EGFR mutation positive non-small cell lung cancer in Singapore

2020 ◽  
Author(s):  
Mohamed Ismail Abdul Aziz ◽  
Wayne Yong Xiang Foo ◽  
Chee Keong Toh ◽  
Wan-Teck Lim ◽  
Kwong Ng
Keyword(s):  
Lung Cancer ◽  
Cost Effectiveness ◽  
Progression Free Survival ◽  
Cost Effective ◽  
Line Treatment ◽  
First Line ◽  
Egfr Mutant ◽  
Nsclc Patients ◽  
The Cost ◽  
First Line Treatment

Abstract Background: Non-small cell lung cancer (NSCLC) accounts for the majority of all lung cancer cases and is usually associated with a poor prognosis. However, targeted therapy with 1st and 2nd generation tyrosine kinase inhibitors (TKIs) has so far improved progression-free survival of epidermal growth factor receptor (EGFR) mutant NSCLC patients. Osimertinib, a third generation EGFR TKI has recently shown improved overall survival in previously untreated EGFR mutant NSCLC patients. We assessed the cost-effectiveness of osimertinib versus standard EGFR TKIs (gefitinib or erlotinib) as first-line treatment for advanced or metastatic EGFR mutant NSCLC patients in Singapore. Methods: A partitioned survival model with three health states (progression-free, progressive disease, and death) was developed from the Singapore healthcare payer perspective. Survival curves from the FLAURA trial were extrapolated beyond trial period over a 10-year time horizon to estimate the underlying progression-free survival and overall survival parametric distributions. Health state utilities were derived from the literature and direct costs were sourced from public healthcare institutions in Singapore. Deterministic and probabilistic sensitivity analyses were conducted to explore the impact of uncertainties and assumptions on cost-effectiveness results. Results: Compared with 1st or 2nd generation TKI, osimertinib had a base-case incremental cost-effectiveness ratio (ICER) of SG$418,839 per quality-adjusted life year gained. One-way sensitivity analysis showed the ICER was most sensitive to time horizon and variations in progression-free utility values. Scenario analyses showed that a 50% reduction in the cost of osimertinib was still associated with a high ICER that was unlikely to be deemed cost effective. Conclusions: Osimertinib is not cost effective as a first-line treatment compared to standard EGFR TKIs in advanced EGFR mutant NSCLC patients in Singapore. The findings from our evaluation, alongside other considerations including the lack of survival benefit in the Asian subgroup of the FLAURA trial, will be useful to inform policy makers on funding decisions for NSCLC treatments in Singapore.

Updated Results of the PRIMA Study Confirms the Benefit of 2-Years Rituximab Maintenance In Follicular Lymphoma Patients Responding to Immunochemotherapy.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1788-1788 ◽  
Author(s):  
Gilles Andre Salles ◽  
John Catalano ◽  
Pierre Feugier ◽  
Fritz C Offner ◽  
Reda Bouabdallah ◽  
...  
Keyword(s):  
Adverse Events ◽  
Follicular Lymphoma ◽  
Research Funding ◽  
Progression Free Survival ◽  
Induction Treatment ◽  
First Line ◽  
Free Survival ◽  
Rituximab Maintenance ◽  
Treatment Characteristics

Abstract Abstract 1788 The GELA-sponsored intergroup PRIMA Phase III study was designed to investigate the potential benefit of 2-years of rituximab maintenance in high tumour burden follicular lymphoma patients responding to one of three non-randomised first line immunochemotherapy treatments. The results of the pre-planned interim analysis with 24 months median follow-up were positive and demonstrated a significant reduction in the risk of progression for patients randomized to rituximab maintenance (Salles et al., ASCO 2010). We present here the updated efficacy and safety results after an additional year of follow-up, when all randomized patients had completed the observation/maintenance period. From December 2004 until April 2007, 1217 patients were enrolled from 223 centres. Complete data are available for 1193 patients who had the following pre-induction treatment characteristics: median age 56 years [range 22–87]; 52% male; 90% Ann Arbor stage III-IV; 33% B symptoms; 55% bone marrow involvement; 4% ECOG performance status >1; 34% elevated LDH; 32% β2-microglobulin≥3mg/L; FLIPI score 0–1 (21%), FLIPI 2 (36%), FLIPI 3–5 (43%). Most patients (74%) received R-CHOP induction (22% R-CVP, 4% R-FCM). Patients responding to induction therapy were stratified based on their immunochemotherapy regimen and response [CR/CRu versus PR], and randomized to observation or rituximab maintenance, 1 infusion (375 mg/m2) every 8 weeks for 2 years. A total of 1018 randomised patients were analyzed according to the ITT principle (513 observation/505 rituximab maintenance). All initial pre-treatment characteristics were well balanced between arms and the response status at time of randomization was CR=39%; CRu=31% and PR=29% (others 1%). After a median follow-up of 36 months, 3-year progression free survival was 60.3% (95% confidence interval [CI] 55.8 – 64.5%) in the observation arm and 78.6% (95% CI 74.7 – 82%) in the rituximab maintenance arm, respectively (stratified Log-Rank, P<.0001; hazard ratio [HR]=0.55, 95% CI 0.44 – 0.68). In pre-planned analyses of patient subgroups categorized by age, sex, FLIPI score, induction chemotherapy and response to induction, the effect of rituximab maintenance was found to be consistent with the overall study results. In a Cox regression multivariate analysis, older age (P=.0013), male sex (P=.013), higher FLIPI group (P<.0001), R-CVP induction treatment (P=.003) and rituximab maintenance (P<.0001) were all significant variables associated with inferior progression free survival. A significant reduction in the number of patients starting a new anti-lymphoma treatment (HR=0.60, 95% CI 0.47 – 0.76) or starting a new chemotherapy (HR=0.62, 95% CI 0.47 – 0.81) was also observed for rituximab maintenance. Regarding response to treatment, 52% of the patients that were in PR at the time of randomization converted to CR or CRu at the end of 2-year maintenance in the rituximab maintenance arm compared to 30% of patients in the observation arm (P=.0001). As a result, 361 out of 482 patients evaluated (75%) in the rituximab maintenance arm were in CR or CRu as compared to 268 out of 491 patients evaluated (55%) in the observation arm (P< .0001). At the time of the data cut-off, 30 patients (6%) had died in the observation arm compared to 26 patients (5%) in the rituximab maintenance arm (HR=0.87, 95% CI 0.51 – 1.47). The most common adverse events reported were infections, which occurred in 24% and 39% of the patients in the observation and rituximab maintenance arms respectively. Grade 3–4 adverse events were reported in 17% of patients in the observation arm and 24% in the rituximab maintenance arm (neutropenia 1% vs 4%; infections 1% vs 4%, respectively) but these lead to treatment discontinuation in only 8 and 19 patients, respectively. In conclusion, after an additional year of follow-up, these data demonstrate a sustained benefit of 2 years of rituximab maintenance therapy after immunochemotherapy, resulting in improved progression free survival and complete response rates. No additional or unexpected toxicities were observed. All randomized patients have an excellent survival to date and longer follow-up will explore factors affecting overall survival in these patients. The PRIMA results indicate that rituximab maintenance should be considered in all follicular lymphoma patients who have responded to first line immunochemotherapy. Disclosures: Salles: Roche: Consultancy, Honoraria. Off Label Use: The use of rituximab maintenance in follicular lymphoma patients. Catalano:Celgene: Research Funding; Roche: Honoraria, Research Funding, Travel Grants. Feugier:roche: Consultancy, Honoraria. Belada:Roche: Consultancy, Honoraria. Tilly:Amgen: Honoraria. Leppa:Roche: Honoraria. Soubeyran:Roche: Honoraria, Research Funding. Hagenbeek:roche: Consultancy. Lister:Allos: Consultancy; Bioconnections: Consultancy; Astra Zeneca: Consultancy; Tenet: Consultancy; GSK: Chairman of Safety Monitoring Committee. Lopez-Guillermo:Roche: Consultancy, Honoraria. Seymour:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau, Travel support; Bayer-Schering: Honoraria, Travel Support.

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