***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: BACKGROUND High-dose melphalan plus autologous stem-cell transplantation ( ASCT ) is the st and ard approach in transplant-eligible patients with newly diagnosed myeloma . Our aims were to compare consolidation with high-dose melphalan plus ASCT versus chemotherapy ( cyclophosphamide and dexamethasone ) plus lenalidomide , and maintenance with lenalidomide plus prednisone versus lenalidomide alone . METHODS We did an open-label , r and omised , multicentre , phase 3 study at 59 centres in Australia , Czech Republic , and Italy . We enrolled transplant-eligible patients with newly diagnosed myeloma aged 65 years or younger . Patients received a common induction with four 28-day cycles of lenalidomide ( 25 mg , days 1 - 21 ) and dexamethasone ( 40 mg , days 1 , 8 , 15 , and 22 ) and subsequent chemotherapy with cyclophosphamide ( 3 g/m(2 ) ) followed by granulocyte colony-stimulating factor for stem-cell mobilisation and collection . Using a 2 × 2 partial factorial design , we r and omised patients to consolidation with either chemotherapy plus lenalidomide ( six cycles of cyclophosphamide [ 300 mg/m(2 ) , days 1 , 8 , and 15 ] , dexamethasone [ 40 mg , days 1 , 8 , 15 , and 22 ] , and lenalidomide [ 25 mg , days 1 - 21 ] ) or two courses of high-dose melphalan ( 200 mg/m(2 ) ) and ASCT . We also r and omised patients to maintenance with lenalidomide ( 10 mg , days 1 - 21 ) plus prednisone ( 50 mg , every other day ) or lenalidomide alone . A simple r and omisation sequence was used to assign patients at enrolment into one of the four groups ( 1:1:1:1 ratio ) , but the treatment allocation was disclosed only when the patient reached the end of the induction and confirmed their eligibility for consolidation . Both the patient and the treating clinician did not know the consolidation and maintenance arm until that time . The primary endpoint was progression-free survival assessed by intention-to-treat . The trial is ongoing and some patients are still receiving maintenance . This study is registered at Clinical Trials.gov , number NCT01091831 . FINDINGS 389 patients were enrolled between July 6 , 2009 , and May 6 , 2011 , with 256 eligible for consolidation ( 127 high-dose melphalan and ASCT and 129 chemotherapy plus lenalidomide ) and 223 eligible for maintenance ( 117 lenalidomide plus prednisone and 106 lenalidomide alone ) . Median follow-up was 52·0 months ( IQR 30·4 - 57·6 ) . Progression-free survival during consolidation was significantly shorter with chemotherapy plus lenalidomide compared with high-dose melphalan and ASCT ( median 28·6 months [ 95 % CI 20·6 - 36·7 ] vs 43·3 months [ 33·2 - 52·2 ] ; hazard ratio [ HR ] for the first 24 months 2·51 , 95 % CI 1·60 - 3·94 ; p<0·0001 ) . Progression-free survival did not differ between maintenance treatments ( median 37·5 months [ 95 % CI 27·8-not evaluable ] with lenalidomide plus prednisone vs 28·5 months [ 22·5 - 46·5 ] with lenalidomide alone ; HR 0·84 , 95 % CI 0·59 - 1·20 ; p=0·34 ) . Fewer grade 3 or 4 adverse events were recorded with chemotherapy plus lenalidomide than with high-dose melphalan and ASCT ; the most frequent were haematological ( 34 [ 26 % ] of 129 patients vs 107 [ 84 % ] of 127 patients ) , gastrointestinal ( six [ 5 % ] vs 25 [ 20 % ] ) , and infection ( seven [ 5 % ] vs 24 [ 19 % ] ) . Haematological serious adverse events were reported in two ( 2 % ) patients assigned chemotherapy plus lenalidomide and no patients allocated high-dose melphalan and ASCT . Non-haematological serious adverse events were reported in 13 ( 10 % ) patients assigned chemotherapy plus lenalidomide and nine ( 7 % ) allocated high-dose melphalan and ASCT . During maintenance , adverse events did not differ between groups . The most frequent grade 3 or 4 adverse events were neutropenia ( nine [ 8 % ] of 117 patients assigned lenalidomide plus prednisone vs 14 [ 13 % ] of 106 allocated lenalidomide alone ) , infection ( eight [ 8 % ] vs five [ 5 % ] ) , and systemic toxicities ( seven [ 6 % ] vs two [ 2 % ] ) . Non-haematological serious adverse events were reported in 13 ( 11 % ) patients assigned lenalidomide plus prednisone versus ten ( 9 % ) allocated lenalidomide alone . Four patients died because of adverse events , three from infections ( two during induction and one during consolidation ) and one because of cardiac toxic effects . INTERPRETATION Consolidation with high-dose melphalan and ASCT remains the preferred option in transplant-eligible patients with multiple myeloma , despite a better toxicity profile with chemotherapy plus lenalidomide . FUNDING Celgene Background High‐dose chemotherapy plus autologous stem‐cell transplantation has been the st and ard treatment for newly diagnosed multiple myeloma in adults up to 65 years of age . However , promising data on the use of combination therapy with lenalidomide , bortezomib , and dexamethasone ( RVD ) in this population have raised questions about the role and timing of transplantation . Methods We r and omly assigned 700 patients with multiple myeloma to receive induction therapy with three cycles of RVD and then consolidation therapy with either five additional cycles of RVD ( 350 patients ) or high‐dose melphalan plus stem‐cell transplantation followed by two additional cycles of RVD ( 350 patients ) . Patients in both groups received maintenance therapy with lenalidomide for 1 year . The primary end point was progression‐free survival . Results Median progression‐free survival was significantly longer in the group that underwent transplantation than in the group that received RVD alone ( 50 months vs. 36 months ; adjusted hazard ratio for disease progression or death , 0.65 ; P<0.001 ) . This benefit was observed across all patient subgroups , including those stratified according to International Staging System stage and cytogenetic risk . The percentage of patients with a complete response was higher in the transplantation group than in the RVD‐alone group ( 59 % vs. 48 % , P=0.03 ) , as was the percentage of patients in whom minimal residual disease was not detected ( 79 % vs. 65 % , P<0.001 ) . Overall survival at 4 years did not differ significantly between the transplantation group and the RVD‐alone group ( 81 % and 82 % , respectively ) . The rate of grade 3 or 4 neutropenia was significantly higher in the transplantation group than in the RVD‐alone group ( 92 % vs. 47 % ) , as were the rates of grade 3 or 4 gastrointestinal disorders ( 28 % vs. 7 % ) and infections ( 20 % vs. 9 % ) . No significant between‐group differences were observed in the rates of treatment‐related deaths , second primary cancers , thromboembolic events , and peripheral neuropathy . Conclusions Among adults with multiple myeloma  , RVD therapy plus transplantation was associated with significantly longer progression‐free survival  than RVD therapy alone , but overall survival did not differ significantly between the two approaches . ( Supported by Celgene and others ; IFM 2009 Study Clinical Trials.gov number , NCT01191060 . In a r and omized , phase 3 study , superior complete/near-complete response ( CR/nCR ) rates and extended progression-free survival were demonstrated with bortezomib-thalidomide-dexamethasone ( VTD ) versus thalidomide-dexamethasone ( TD ) as induction therapy before , and consolidation after , double autologous stem cell transplantation for newly diagnosed myeloma patients ( intention-to-treat analysis ; VTD , n = 236 ; TD , n = 238 ) . This per- protocol analysis ( VTD , n = 160 ; TD , n = 161 ) specifically assessed the efficacy and safety of consolidation with VTD or TD . Before starting consolidation , CR/nCR rates were not significantly different in the VTD ( 63.1 % ) and TD arms ( 54.7 % ) . After consolidation , CR ( 60.6 % vs 46.6 % ) and CR/nCR ( 73.1 % vs 60.9 % ) rates were significantly higher for VTD-treated versus TD-treated patients . VTD consolidation significantly increased CR and CR/nCR rates , but TD did not ( McNemar test ) . With a median follow-up of 30.4 months from start of consolidation , 3-year progression-free survival was significantly longer for the VTD group ( 60 % vs 48 % for TD ) . Grade 2 or 3 peripheral neuropathy ( 8.1 % vs 2.4 % ) was more frequent with VTD ( grade 3 , 0.6 % ) versus TD consolidation . The superior efficacy of VTD versus TD as induction was retained despite readministration as consolidation therapy after double autologous transplantation . VTD consolidation therapy significantly contributed to improved clinical outcomes observed for patients r and omly assigned to the VTD arm of the study . The study is registered at www . clinical trials.gov as # NCT01134484 The Nordic Myeloma Study Group conducted an open r and omized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation ( ASCT ) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma . Overall , 370 patients were central ly r and omly assigned 3 months after ASCT to receive 20 doses of bortezomib given during 21 weeks or no consolidation . The hypothesis was that consolidation therapy would prolong progression-free survival ( PFS ) . The PFS after r and omization was 27 months for the bortezomib group compared with 20 months for the control group ( P = .05 ) . Fifty-one of 90 patients in the treatment group compared with 32 of 90 controls improved their response after r and omization ( P = .007 ) . No difference in overall survival was seen . Fatigue was reported more commonly by the bortezomib-treated patients in self-reported quality -of-life ( QOL ) question naires , whereas no other major differences in QOL were recorded between the groups . Consolidation therapy seemed to be beneficial for patients not achieving at least a very good partial response ( VGPR ) but not for patients in the ≥ VGPR category at r and omization . Consolidation with bortezomib after ASCT in bortezomib-naive patients improves PFS without interfering with QOL . This trial was registered at www . clinical trials.gov as # NCT00417911 BACKGROUND High-dose chemotherapy with autologous stem-cell transplantation is a st and ard treatment for young patients with multiple myeloma . Residual disease is almost always present after transplantation and is responsible for relapse . This phase 3 , placebo-controlled trial investigated the efficacy of lenalidomide maintenance therapy after transplantation . METHODS We r and omly assigned 614 patients younger than 65 years of age who had nonprogressive disease after first-line transplantation to maintenance treatment with either lenalidomide ( 10 mg per day for the first 3 months , increased to 15 mg if tolerated ) or placebo until relapse . The primary end point was progression-free survival . RESULTS Lenalidomide maintenance therapy improved median progression-free survival ( 41 months , vs. 23 months with placebo ; hazard ratio , 0.50 ; P<0.001 ) . This benefit was observed across all patient subgroups , including those based on the β(2)-microglobulin level , cytogenetic profile , and response after transplantation . With a median follow-up period of 45 months , more than 70 % of patients in both groups were alive at 4 years . The rates of grade 3 or 4 peripheral neuropathy were similar in the two groups . The incidence of second primary cancers was 3.1 per 100 patient-years in the lenalidomide group versus 1.2 per 100 patient-years in the placebo group ( P=0.002 ) . Median event-free survival ( with events that included second primary cancers ) was significantly improved with lenalidomide ( 40 months , vs. 23 months with placebo ; P<0.001 ) . CONCLUSIONS Lenalidomide maintenance after transplantation significantly prolonged progression-free and event-free survival among patients with multiple myeloma . Four years after r and om 
    Output:
    
Our data suggest that , in NDMM patients treated with upfront ASCT , post-transplant consolidation may improve depth of response , but does not add to OS or PFS , compared to lenalidomide maintenance alone .