***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Phase 2 studies suggest that the monoclonal antibody rituximab may improve the prognosis of patients with follicular lymphoma ( FL ) when it is added to chemotherapy . In the current study , 428 patients with untreated , advanced-stage FL were r and omly assigned for therapy with cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) alone ( n = 205 ) or CHOP combined with rituximab ( R-CHOP ) ( n = 223 ) . R-CHOP reduced the relative risk for treatment failure by 60 % and significantly prolonged the time to treatment failure ( P < .001 ) . In addition , a significantly higher overall response rate ( 96 % vs 90 % ; P = .011 ) and a prolonged duration of remission ( P = .001 ) were achieved . In spite of a relatively short observation time , these beneficial effects even translated to superior overall survival ( P = .016 ) , with 6 deaths in the R-CHOP group compared with 17 deaths in the CHOP group within the first 3 years . The predominant treatment-related adverse effect was myelosuppression . Severe granulocytopenia was more frequently observed after R-CHOP ( 63 % vs 53 % ; P = .01 ) . However , severe infections were rare and of similar frequency after R-CHOP and CHOP ( 5 % and 7 % ) . Hence , adding rituximab to CHOP significantly improves the outcome for patients with previously untreated advanced-stage FL and does not induce major adverse effects Abstract Objectives The r and omized phase 3 PRIMA trial established that 2 years of rituximab maintenance therapy after attaining disease response to immunochemotherapy as first-line treatment of follicular lymphoma , reduced the risk of disease progression , compared with observation , without adversely affecting patient-reported quality of life ( QoL ) . We now report additional analyses of symptom burden and toxicity . Methods Symptom burden was measured by the European Organisation for Research and Treatment of Cancer Quality of Life Question naire – Core 30 items . The proportion of patients with worsening , no change , or improvement in symptoms from maintenance baseline was compared between  rituximab maintenance and observation groups with Pearson χ2 tests . Improvement in symptoms after 1 and 2 years of maintenance was further analyzed using generalized mixed models . The adverse event ( AE ) rate was calculated from the toxicity checklist at each visit to explore the frequency and timing of the toxicity AE in each treatment arm . The study protocol was approved by local ethics committees and is registered at Clinical Trials.gov under NCT00140582 . Results Being tired , needing to rest , feeling weak , and trouble sleeping were the most frequently reported symptoms at the end of immunochemotherapy . By the end of maintenance , notable improvement was seen for fatigue symptoms , trouble sleeping , shortness of breath , lack of appetite , and nausea , with no significant difference in QoL symptoms between the rituximab maintenance and observation groups . The rate of AEs was low , and hematologic toxicity induced during chemotherapy treatment improved in both rituximab maintenance and observation groups . Discussion These results indicated that rituximab maintenance did not negatively impact disease- or treatment-related symptoms The addition of rituximab to cyclophosphamide , vincristine and prednisolone ( CVP ) for advanced follicular lymphoma increases median time to progression by 17 months . A US societal cost-effectiveness of R-CVP versus CVP is estimated for a representative 50-year-old patient .  Progression-free survival ( PFS ) and overall survival are based on a r and omized Phase III trial . Costs are estimated using Medicare reimbursement rates and published drug price data , and include drug and administration costs , adverse events , treatment of relapses , and end-of-life care . Utility estimates are derived from the literature and a 3 % discount rate is employed . Mean overall survival is projected to be 1.51 years longer for patients assigned to R-CVP versus CVP . The cost per quality -adjusted year of life gained is $ 28,565 . The utility associated with stable or progressive disease and the unit drug cost of rituximab most influence the findings . The cost-effectiveness ratio of R-CVP compared with CVP is projected to be cost-effective in the United States under a range of sensitivity analyses Background Follicular lymphoma ( FL ) is the second most common type of lymphoid cancer in Western Europe . Objective The aim of this study was to evaluate the cost utility of rituximab – bendamustine treatment compared with R-CHOP ( rituximab , cyclophosphamide , doxorubicin , vincristine and prednisone ) treatment as a first-line therapy for patients with advanced FL in Spain . Methods A Markov model was developed to estimate the cost effectiveness of rituximab – bendamustine compared with R-CHOP as first-line treatment for patients with advanced FL in the Spanish National Health System ( NHS ) . Transitions between health states ( progression-free , including induction and maintenance ; first relapse ; second relapse ; and death ) were allowed for the patient cohort in 4-week-long cycles . Clinical data for the extrapolation of progression-free survival curves were obtained from r and omized trials . Mortality rates and utilities were obtained from the literature . Outcomes were measured as quality -adjusted life-years ( QALYs ) . The total costs ( € , 2013 ) included drug costs ( ex-factory prices with m and atory deductions ) , disease management costs and adverse event-associated costs . Costs and outcomes were discounted at a 3 % annual rate . Probabilistic sensitivity analysis was performed using 10,000 Monte Carlo simulations to assess the model robustness . Results Treatment and administration costs during the induction phase were higher for rituximab – bendamustine ( € 17,671 ) than for R-CHOP ( € 11,850 ) . At the end of the 25-year period , the rituximab – bendamustine first-line strategy had a total cost of € 68,357 compared with € 69,528 for R-CHOP  . Health benefits were higher for rituximab – bendamustine treatment ( 10.31 QALYs ) than for R-CHOP treatment ( 9.82 QALYs ) . In the probabilistic analysis , rituximab – bendamustine was the dominant strategy over treatment with R-CHOP in 53.4 % of the simulations . Conclusion First-line therapy with rituximab – bendamustine in FL patients was the dominant strategy over treatment with R-CHOP ; it showed cost savings and higher health benefits for the Spanish NHS BACKGROUND Patients with indolent non-Hodgkin lymphoma who fail to achieve adequate disease control with rituximab-based treatment have few treatment options and a poor prognosis . We aim ed to assess a combination of obinutuzumab ( GA101 ) , a novel glyco-engineered type II anti-CD20 monoclonal antibody , and bendamustine in this patient population . METHODS In this open-label , r and omised , phase 3 study ( GADOLIN ) , patients aged 18 years or older with histologically documented , CD20-positive indolent non-Hodgkin lymphoma refractory to rituximab were enrolled at 83 hospital and community sites in 14 countries in Europe , Asia , and North and Central America . Patients were r and omly assigned ( 1:1 ) using a hierarchical dynamic r and omisation scheme stratified by indolent non-Hodgkin lymphoma subtype , rituximab-refractory type , number of previous therapies , and geographical region , to receive induction treatment ( six 28-day cycles ) with obinutuzumab plus bendamustine or bendamustine monotherapy , both given intravenously . Obinutuzumab plus bendamustine dosing was obinutuzumab 1000 mg ( days 1 , 8 , and 15 , cycle 1 ; day 1 , cycles 2 - 6 ) plus bendamustine 90 mg/m(2 ) per day ( days 1 and 2 , cycles 1 - 6 ) , and bendamustine monotherapy dosing was 120 mg/m(2 ) per day ( days 1 and 2 , all cycles ) . Non-progressing patients in the obinutuzumab plus bendamustine group received obinutuzumab maintenance ( 1000 mg every 2 months ) for up to 2 years . The primary endpoint was progression-free survival in all r and omised patients , as assessed by an independent review committee . Safety was assessed in all patients who received any amount of obinutuzumab or bendamustine . This study is registered with Clinical Trials.gov , number NCT01059630 , and has stopped recruiting patients . FINDINGS Between April 15 , 2010 , and Sept 1 , 2014 , when the study was stopped after a pre-planned interim analysis , 396 patients were r and omly assigned ( 194 to obinutuzumab plus bendamustine and 202 to bendamustine monotherapy ) . After a median follow-up time of 21·9 months ( IQR 12·1 - 31·0 ) in the obinutuzumab plus bendamustine group and 20·3 months ( 9·5 - 29·7 ) in the bendamustine monotherapy group , progression-free survival was significantly longer with obinutuzumab plus bendamustine ( median not reached [ 95 % CI 22·5 months-not estimable ] ) than with bendamustine monotherapy ( 14·9 months [ 12·8 - 16·6 ] ; hazard ratio 0·55 [ 95 % CI 0·40 - 0·74 ] ; p=0·0001 ) . Grade 3 - 5 adverse events occurred in 132 ( 68 % ) of 194 patients in the obinutuzumab plus bendamustine group and in 123 ( 62 % ) of 198 patients in the bendamustine monotherapy group . The most frequent grade 3 or worse adverse events were neutropenia ( 64 [ 33 % ] in the obinutuzumab plus bendamustine group vs 52 [ 26 % ] in the bendamustine  monotherapy group ) , thrombocytopenia ( 21 [ 11 % ] vs 32 [ 16 % ] ) , anaemia ( 15 [ 8 % ] vs 20 [ 10 % ] ) and infusion-related reactions ( 21 [ 11 % ] vs 11 [ 6 % ] ) . Serious adverse events occurred in 74 patients ( 38 % ) in the obinutuzumab plus bendamustine group and in 65 patients ( 33 % ) in the bendamustine monotherapy group , and deaths due to adverse events occurred in 12 patients ( 6 % ) and 12 patients ( 6 % ) , respectively . Three ( 25 % ) of 12 adverse event-related deaths in the obinutuzumab plus bendamustine group and five ( 42 % ) of 12 in the bendamustine monotherapy group were treatment related . INTERPRETATION Obinutuzumab plus bendamustine followed by obinutuzumab maintenance has improved efficacy over bendamustine monotherapy in rituximab-refractory patients with indolent non-Hodgkin lymphoma , with manageable toxicity , and is a new treatment option for patients who have relapsed after or are no longer responding to rituximab-based therapy . FUNDING F Hoffmann-La Roche We evaluated the role of rituximab ( R ) both in remission induction and maintenance treatment of relapsed/resistant follicular lymphoma ( FL ) . A total of 465 patients were r and omized to induction with 6 cycles of cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) ( every 3 weeks ) or R-CHOP ( R : 375 mg/m(2 ) intravenously , day 1 ) . Those in complete remission ( CR ) or partial remission ( PR ) were r and omized to maintenance with R ( 375 mg/m(2 ) intravenously once every 3 months for a maximum of 2 years ) or observation . R-CHOP induction yielded an increased overall response rate ( CHOP , 72.3 % ; R-CHOP , 85.1 % ; P < .001 ) and CR rate ( CHOP , 15.6 % ; R-CHOP , 29.5 % ; P < .001 ) . Median progression-free survival ( PFS ) from first r and omization was 20.2 months after CHOP versus 33.1 months after R-CHOP ( hazard ratio [ HR ] , 0.65 ; P < .001 ) . Rituximab maintenance yielded a median PFS from second r and omization of 51.5 months versus 14.9 months with observation ( HR , 0.40 ; P < .001 ) . Improved PFS was found both after induction with CHOP ( HR , 0.30 ; P < .001 ) and R-CHOP ( HR , 0.54 ; P = .004 ) . R maintenance also improved overall survival from second r and omization : 85 % at 3 years versus 77 % with observation ( HR , 0.52 ; P = .011 ) . This is the first trial showing that in relapsed/resistant FL rituximab 
    Output:
    
Markov models were the most utilised cost-effectiveness model .
We found a small body of evidence of quality of life , and potentially cost-effective treatment options for FL ; however , no evidence was reported on MZL specifically .