***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: Abstract In the MM-015 trial , melphalan – prednisone – lenalidomide followed by lenalidomide maintenance ( MPR-R ) significantly prolonged progression-free survival versus melphalan – prednisone ( MP ) in newly diagnosed patients with multiple myeloma aged ≥ 65 years . Health-related quality of life ( HRQoL ) , a secondary endpoint of MM-015 , was also improved with MPR-R. This sub- analysis evaluated the impact of individual predictive factors on HRQoL. Patients completed HRQoL question naires at baseline , every third cycle and at progressive disease (PD)/treatment discontinuation . In a mixed-effects model female gender , advanced age and PD negatively affected HRQoL while better treatment responses showed positive effects . Compared to PD , HRQoL during MPR-R treatment was statistically significantly better in two of six preselected domains both of which were also clinical ly meaningful . HRQoL scores at end of treatment were all either improved or not statistically significantly different versus baseline . In conclusion , continuous treatment with MPR-R , which delays PD , appears to be associated with clinical ly meaningful improvements in We have carried out the largest r and omised trial to date of newly diagnosed myeloma patients , in which lenalidomide has been used as an induction and maintenance treatment option and here report its impact on second primary malignancy ( SPM ) incidence and pathology . After review , 104 SPMs were confirmed in 96 of 2732 trial patients . The cumulative incidence of SPM was 0.7 % ( 95 % confidence interval ( CI ) 0.4–1.0 % ) , 2.3 % ( 95 % CI 1.6–2.7 % ) and 3.8 % ( 95 % CI 2.9–4.6 % ) at 1 , 2 and 3 years , respectively . Patients receiving maintenance lenalidomide  had a significantly higher SPM incidence overall ( P=0.011 ) . Age is a risk factor with the highest SPM incidence observed in transplant non-eligible patients aged > 74 years receiving lenalidomide maintenance .  The 3-year cumulative incidence in this group was 17.3 % ( 95 % CI 8.2–26.4 % ) , compared with 6.5 % ( 95 % CI 0.2–12.9 % ) in observation only patients ( P=0.049 ) . There was a low overall incidence of haematological SPM ( 0.5 % ) . The higher SPM incidence in patients receiving lenalidomide maintenance therapy , especially in advanced age , warrants ongoing monitoring although the benefit on survival is likely to outweigh risk We compared thalidomide-dexamethasone ( TD ) with melphalan-prednisolone ( MP ) in 289 elderly patients with multiple myeloma ( MM ) . Patients received either thalidomide 200 mg plus dexamethasone 40 mg , days 1 to 4 and 15 to 18 on even cycles and days 1 to 4 on odd cycles , during a 28-day cycle or to melphalan 0.25 mg/kg and prednisolone 2 mg/kg orally on days 1 to 4 during a 28- to 42-day cycle . Patients achieving stable disease or better were r and omly assigned to maintenance therapy with either thalidomide 100 mg daily and 3 MU interferon alpha-2b thrice weekly or to 3 MU interferon alpha-2b thrice weekly only . TD result ed in a higher proportion of complete and very good remissions ( 26 % vs 13 % ; P= .006 ) and overall responses ( 68 % vs 50 % ; P= .002 ) compared with MP . Time to progression ( 21.2 vs 29.1 months ; P= .2 ) , and progression-free survival was similar ( 16.7 vs 20.7 months ; P= .1 ) , but overall survival was significantly shorter in the TD group ( 41.5 vs 49.4 months ; P= .024 ) . Toxicity was higher with TD , particularly in patients older than 75 years with poor performance status . The study was registered at Clinical Trials.gov as NCT00205751 Because interleukin-6 ( IL-6 ) is considered important in the proliferation of early multiple myeloma ( MM ) , we hypothesized that the addition of the anti-IL-6 monoclonal antibody siltuximab to the bortezomib-melphalan-prednisone ( VMP ) regimen would improve outcomes in transplant-ineligible patients with newly diagnosed MM . One hundred and six patients were r and omized to receive 9 cycles of VMP or VMP plus siltuximab ( 11 mg/kg every 3 weeks ) followed by siltuximab maintenance . Baseline characteristics were well balanced except for immunoglobulin A subtype and 17p deletions . With a complete response ( CR ) rate of 27 % on siltuximab plus VMP ( S+VMP ) and 22 % on VMP , the study did not confirm its hypothesis that the addition of siltuximab would increase the CR rate by at least 10 % . Overall response rate was 88 % on S+VMP and 80 % on VMP , and at least very good partial response rates were 71 % and 51 % ( P = .0382 ) , respectively . Median progression-free survival ( 17 months ) and 1-year overall survival ( 88 % ) were identical in the 2 arms . Grade ≥3 adverse-event incidence was 92 % on S+VMP and 81 % on VMP ( P = .09 ) , with trends toward more hematologic events and infections on S+VMP . Maintenance therapy with siltuximab was well tolerated . In conclusion , the addition of siltuximab to VMP did not improve the CR rate or long-term outcomes . This study was registered at http:// clinical trials.gov as # NCT00911859 Oral melphalan and prednisone remain an effective and tolerable treatment for patients with multiple myeloma . For approximately 40 years , this combination has been the st and ard of care for patients not proceeding to stem cell transplant . Within the last 10 years , new agents have been found to be efficacious in the relapsed/refractory setting . Within the last year , two trials of added thalidomide in the newly diagnosed setting have demonstrated outcomes superior to those achieved with melphalan and prednisone alone . This improved outcome comes at the cost of increased toxicity . The National Cancer Institute of Canada Clinical Trials Group ( ncic ctg ) has recently developed a r and omized phase ii trial ( MY.11 ) that uses a combination of lenalidomide with melphalan for patients with newly diagnosed multiple myeloma .  Lenalidomide is a thalidomide analogue and , like thalidomide , is thought to work through immunomodulatory effects . It was shown to have activity in patients with relapsed or refractory disease and , in combination with dexamethasone , is superior to dexamethasone alone . Lenalidomide holds promise as a more effective and potentially less toxic derivative of thalidomide . Experience with lenalidomide in combination with chemotherapy is very limited , and the purpose of MY.11 is to establish tolerability and to gain knowledge about efficacy . The information gained from MY.11 is expected to help inform dosing levels and schedules for a large phase iii trial being developed by the Eastern Cooperative Oncology Group that will include participation by the ncic ctg Purpose This analysis of the FIRST trial in patients with newly diagnosed multiple myeloma ( MM ) ineligible for stem-cell transplantation examined up date d outcomes and impact of patient age . Patients and Methods Patients with untreated symptomatic MM were r and omly assigned at a one-to-one-to-one ratio to lenalidomide plus low-dose dexamethasone until disease progression ( Rd continuous ) , Rd for 72 weeks ( 18 cycles ; Rd18 ) , or melphalan , prednisone , and thalidomide ( MPT ; 72 weeks ) , stratified by age ( ≤ 75 v > 75 years ) , disease stage ( International Staging System stage I/II v III ) , and country . The primary end point was progression-free survival . Rd continuous and MPT were primary comparators . Results Between August 21 , 2008 , and March 7 , 2011 , 1,623 patients were enrolled ( Rd continuous , n = 535 ; Rd18 , n = 541 ; MPT , n = 547 ) , including 567 ( 35 % ) age older than 75 years .  Higher rates of advanced-stage disease and renal impairment were observed in patients older than 75 versus 75 years of age or younger . Rd continuous reduced the risk of progression or death compared with MPT by 31 % ( hazard ratio [ HR ] , 0.69 ; 95 % CI , 0.59 to 0.80 ; P < .001 ) overall , 36 % ( HR , 0.64 ; 95 % CI , 0.53 to 0.77 ; P < .001 ) in patients age 75 years or younger , and 20 % ( HR , 0.80 ; 95 % CI , 0.62 to 1.03 ; P = .084 ) in those age older than 75 years . Median overall survival was longer with Rd continuous than with MPT , including a 14-month difference in patients age older than 75 years . Progression-free survival with Rd18 was similar to that with MPT , and overall survival with Rd18 was marginally inferior to that with Rd continuous . Rates of grade 3 to 4 treatment-emergent adverse events were similar for Rd continuous-treated patients age 75 years or older and those age older than 75 years ; however , older patients had more frequent lenalidomide dose reductions . Conclusion Results support Rd continuous treatment as a new st and ard of care for stem-cell transplantation-ineligible patients with newly diagnosed MM of all ages Bortezomib plus melphalan and prednisone ( VMP ) and lenalidomide plus low-dose dexamethasone ( Rd ) are 2 st and ards of care for elderly untreated multiple myeloma ( MM ) patients . We planned to use VMP and Rd for 18 cycles in a sequential or alternating scheme . Patients ( 233 ) with untreated MM , > 65 years , were r and omized to receive 9 cycles of VMP followed by 9 cycles of Rd ( sequential scheme ; n = 118 ) vs 1 cycle of VMP followed by 1 cycle of Rd , and so on , up to 18 cycles ( alternating scheme ; n = 115 ) . VMP consisted of one 6-week cycle of bortezomib using a biweekly schedule , followed by eight 5-week cycles of once-weekly VMP . Rd included nine 4-week cycles of Rd . The primary end points were 18-month progression free survival ( PFS ) and safety profile of both schemes . The 18-month PFS was 74 % and 80 % in the sequential and alternating arms , respectively ( P = .21 ) . The sequential and alternating groups exhibited similar hematologic and nonhematologic toxicity . Both arms yielded similar complete response rate ( 42 % and 40 % ) , median PFS ( 32 months vs 34 months , P = .65 ) , and 3-year overall survival ( 72 % vs 74 % , P = .63 ) . The benefit of both schemes was remarkable in patients aged 65 to 75 years . In addition , achieving complete and immunophenotypic response was associated with better outcome . The present approach , based on VMP and Rd , is associated with high efficacy and acceptable toxicity profile with no differences between the sequential and alternating regimens . This trial was registered at www . clinical trials.gov as # NCT00443235 Thalidomide with melphalan/prednisone ( MPT ) was defined as st and ard treatment in elderly patients with multiple myeloma ( MM ) based on five r and omized trials . In one of these trials , HOVON49 , a prospect i ve health-related quality -of-life ( HRQoL ) study was initiated in order to assess the impact of thalidomide on QoL. Patients aged > 65 years with newly diagnosed MM were r and omized to receive melphalan plus prednisone ( MP ) or MPT , followed by thalidomide maintenance in the MPT arm . Two hundred eighty-four patients were included in this side study ( MP , n = 149 ; MPT n = 135 ) . HRQoL was assessed with the EORTC Core QoL Question naire ( QLQ-C30 ) and the myeloma-specific module ( QLQ-MY24 ) at baseline and at predetermined intervals during treatment . The QLQ-C30 subscales physical function ( P = 0.044 ) and constipation ( P < 0.001 ) showed an improvement during induction in favour of the MP arm . During thalidomide maintenance , the scores for the QLQ-MY24 paraesthesia became significantly higher in the MPT arm ( P<0.001 ) . The QLQ-C30 subscales pain ( P = 0.12 ) , insomnia ( P = 0.068 ) , appetite loss ( P = 0.074 ) and the QLQ-MY24 item sick ( P = 0.086 ) scored marginally better during thalidomide maintenance . The overall QoL-scale QLQ-C30-HR 
    Output:
    
Based on our four pre-selected comparisons of interest , continuous treatment with VRD had the largest survival benefit compared with MP , while RD and TMP also probably considerably increase survival .
However , treatment combinations of V , R , and T also substantially increase the incidence of AEs , and lead to a higher risk of treatment discontinuation .