***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: In this proof-of-concept , open-label , phase 2 study , patients with relapsed/refractory multiple myeloma ( RRMM ) received elotuzumab with bortezomib and dexamethasone ( EBd ) or bortezomib and dexamethasone ( Bd ) until disease progression/unacceptable toxicity . Primary endpoint was progression-free survival ( PFS ) ; secondary /exploratory endpoints included overall response rate ( ORR ) and overall survival ( OS ) . Two-sided 0.30 significance level was specified ( 80 % power , 103 events ) to detect hazard ratio ( HR ) of 0.69 . Efficacy and safety analyses were performed on all r and omized patients and all treated patients , respectively . Of 152 r and omized patients ( 77 EBd , 75 Bd ) , 150 were treated ( 75 EBd , 75 Bd ) . PFS was greater with EBd vs Bd ( HR , 0.72 ; 70 % confidence interval [ CI ] , 0.59 - 0.88 ; stratified log-rank P = .09 ) ; median PFS was longer with EBd ( 9.7 months ) vs Bd ( 6.9 months ) . In an up date d analysis , EBd-treated patients homozygous for the high-affinity FcγRIIIa allele had median PFS of 22.3 months vs 9.8 months in EBd-treated patients homozygous for the low-affinity allele . ORR was 66 % ( EBd ) vs 63 % ( Bd ) . Very good partial response or better occurred in 36 % of patients ( EBd ) vs 27 % ( Bd ) . Early OS results , based on 40 deaths , revealed an HR of 0.61 ( 70 % CI , 0.43 - 0.85 ) . To date , 60 deaths have occurred ( 28 EBd , 32 Bd ) . No additional clinical ly significant adverse events occurred with EBd vs Bd . Grade 1/2 infusion reaction rate was low ( 5 % EBd ) and mitigated with premedication . In patients with RRMM , elotuzumab , an immunostimulatory antibody , appears to provide clinical benefit without added clinical ly significant toxicity when combined with Bd vs Bd alone . Registered to Clinical Trials.gov as NCT01478048 BACKGROUND We aim ed to assess efficacy and tolerability of vorinostat in combination with bortezomib for treatment of patients with relapsed or refractory multiple myeloma . METHODS In our r and omised , double-blind , placebo-controlled , phase 3 trial , we enrolled adults ( ≥18 years ) at 174 university hospitals in 31 countries worldwide . Eligible patients had to have non-refractory multiple myeloma that previously responded to treatment ( one to three regimens ) but were currently progressing , ECOG performance statuses of 2 or less , and no continuing toxic effects from previous treatment . We excluded patients with known resistance to bortezomib . We r and omly allocated patients ( 1:1 ) using an interactive voice response system to receive 21 day cycles of bortezomib ( 1·3 mg/m(2 ) intravenously on days 1 , 4 , 8 , and 11 ) in combination with oral vorinostat ( 400 mg ) or matching placebo once-daily on days 1 - 14 . We stratified patients by baseline tumour stage ( International Staging System stage 1 or stage ≥2 ) , previous bone-marrow transplantation ( yes or no ) , and number of previous regimens ( 1 or ≥2 ) . The primary endpoint was progression-free survival ( PFS ) in the intention-to-treat population . We assessed adverse events in all patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number 00773747 . FINDINGS Between Dec 24 , 2008 , and Sept 8 , 2011 , we r and omly allocated 317 eligible patients to the  vorinostat group ( 315 of whom received at least one dose ) and 320 to the placebo group ( all of whom received at least one dose ) . Median PFS was 7·63 months ( 95 % CI 6·87 - 8·40 ) in the vorinostat group and 6·83 months ( 5·67 - 7·73 ) in the placebo group ( hazard ratio [ HR ] 0·77 , 95 % CI 0·64 - 0·94 ; p=0·0100 ) . 312 ( 99 % ) of 315 patients in the vorinostat group and 315 ( 98 % ) of 320 patients in the placebo group had adverse events ( 300 [ 95 % ] adverse events in the vorinostat group and 282 [ 88 % ] in the control group were regarded as related to treatment ) . The most common grade 3 - 4 adverse events were thrombocytopenia ( 143 [ 45 % ] patients in the vorinostat group vs 77 [ 24 % ] patients in the placebo group ) , neutropenia ( 89 [ 28 % ] vs 80 [ 25 % ] ) , and anaemia ( 53 [ 17 % ] vs 40 [ 13 % ] ) . INTERPRETATION Although the combination of vorinostat and bortezomib prolonged PFS relative to bortezomib and placebo , the clinical relevance of the difference in PFS between the two groups is not clear . Different treatment schedules of bortezomib and vorinostat might improve tolerability and enhance activity . FUNDING Merck BACKGROUND Daratumumab showed promising efficacy alone and with lenalidomide and dexamethasone in a phase 1 - 2 study involving patients with relapsed or refractory multiple myeloma . METHODS In this phase 3 trial , we r and omly assigned 569 patients with multiple myeloma who had received one or more previous lines of therapy to receive lenalidomide and dexamethasone either alone ( control group ) or in combination with daratumumab ( daratumumab group ) . The primary end point was progression-free survival . RESULTS At a median follow-up of 13.5 months in a protocol -specified interim analysis , 169 events of disease progression or death were observed ( in 53 of 286 patients [ 18.5 % ] in the daratumumab group vs. 116 of 283 [ 41.0 % ] in the control group ; hazard ratio , 0.37 ; 95 % confidence interval [ CI ] , 0.27 to 0.52 ; P<0.001 by stratified log-rank test ) . The Kaplan-Meier rate of progression-free survival at 12 months was 83.2 % ( 95 % CI , 78.3 to 87.2 ) in the daratumumab group , as compared with 60.1 % ( 95 % CI , 54.0 to 65.7 ) in the control group . A significantly higher rate of overall response was observed in the daratumumab group than in the control group ( 92.9 % vs. 76.4 % , P<0.001 ) , as was a higher rate of complete response or better ( 43.1 % vs. 19.2 % , P<0.001 ) . In the daratumumab group , 22.4 % of the patients had results below the threshold for minimal residual disease ( 1 tumor cell per 105 white cells ) , as compared with 4.6 % of those in the control group ( P<0.001 ) ; results below the threshold for minimal residual disease were associated with improved outcomes . The most common adverse events of grade 3 or 4 during treatment were neutropenia ( in 51.9 % of the patients in the daratumumab group vs. 37.0 % of those in the control group ) , thrombocytopenia ( in 12.7 % vs. 13.5 % ) , and anemia ( in 12.4 % vs. 19.6 % ) . Daratumumab-associated infusion-related reactions occurred in 47.7 % of the patients and were mostly of grade 1 or 2 . CONCLUSIONS The addition of daratumumab to lenalidomide and dexamethasone significantly lengthened progression-free survival among patients with relapsed or refractory multiple myeloma .  Daratumumab was associated with infusion-related reactions and a higher rate of neutropenia than the control therapy . ( Funded by Janssen Research and Development ; POLLUX Clinical Trials.gov number , NCT02076009 . ) BACKGROUND Panobinostat is a potent oral pan-deacetylase inhibitor that in pre clinical studies has synergistic anti-myeloma activity when combined with bortezomib and dexamethasone . We aim ed to compare panobinostat , bortezomib , and dexamethasone with placebo , bortezomib , and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma . METHODS PANORAMA1 is a multicentre , r and omised , placebo-controlled , double-blind phase 3 trial of patients with relapsed or relapsed and refractory multiple myeloma who have received between one and three previous treatment regimens . Patients were r and omly assigned ( 1:1 ) via an interactive web-based and voice response system , stratified by number of previous treatment lines and by previous use of bortezomib , to receive 21 day cycles of placebo or panobinostat ( 20 mg ; on days 1 , 3 , 5 , 8 , 10 , 12 , orally ) , both in combination with bortezomib ( 1·3 mg/m(2 ) on days 1 , 4 , 8 , 11 , intravenously ) and dexamethasone ( 20 mg on days 1 , 2 , 4 , 5 , 8 , 9 , 11 , 12 , orally ) . Patients , physicians , and the investigators who did the data analysis were masked to treatment allocation ; crossover was not permitted . The primary endpoint was progression-free survival ( in accordance with modified European Group for Blood and Marrow Transplantation criteria and based on investigators ' assessment ) and was analysed by intention to treat . The study is ongoing , but no longer recruiting , and is registered at Clinical Trials.gov , number NCT01023308 . FINDINGS 768 patients were enrolled between Jan 21 , 2010 , and Feb 29 , 2012 , with 387 r and omly assigned to panobinostat , bortezomib , and dexamethasone and 381 to placebo , bortezomib , and dexamethasone . Median follow-up was 6·47 months ( IQR 1·81 - 13·47 ) in the panobinostat group and 5·59 months ( 2·14 - 11·30 ) in the placebo group . Median progression-free survival was significantly longer in the panobinostat group than in the placebo group ( 11·99 months [ 95 % CI 10·33 - 12·94 ] vs 8·08 months [ 7·56 - 9·23 ] ; hazard ratio [ HR ] 0·63 , 95 % CI 0·52 - 0·76 ; p<0·0001 ) . Overall survival data are not yet mature , although at the time of this analysis , median overall survival was 33·64 months ( 95 % CI 31·34-not estimable ) for the panobinostat group and 30·39 months ( 26·87-not estimable ) for the placebo group ( HR 0·87 , 95 % CI 0·69 - 1·10 ; p=0·26 ) . The proportion of patients achieving an overall response did not differ between treatment groups ( 235 [ 60·7 % , 95 % CI 55·7 - 65·6 ] for panobinostat vs 208 [ 54·6 % , 49·4 - 59·7 ] for placebo ; p=0·09 ) ; however , the proportion of patients with a complete or near complete response was significantly higher in the panobinostat group than in the placebo group ( 107 [ 27·6 % , 95 % CI 23·2 - 32·4 ] vs 60 [ 15·7 % , 12·2 - 19·8 ] ; p=0·00006 ) . Minimal responses were noted in 23 ( 6 % ) patients in the panobinostat group and in 42 ( 11 % ) in the placebo group . Median duration of response ( partial response or better ) was 13·14 months ( 95 % CI 11·76 - 14·92 ) in the panobinostat group and 10·87 months ( 9·23 - 11·76 ) in the placebo group , and median time to response ( partial response or better ) was 1·51 months ( 1·41 - 1·64 ) in the panobinostat group and 2·00 months ( 1·61 - 2·79 ) in the placebo group . Serious adverse events were reported in 228 ( 60 % 
    Output:
    
Pairwise meta-analyses showed that a 3-drug regimen ( bortezomib- or IMiD-based ) was superior to a 2-drug regimen in progression-free-survival ( PFS ) and overall response rate ( ORR ) .
NMA showed that an IMiD backbone associated with anti-MM monoclonal antibodies ( mAbs ) ( preferably ) or proteasome inhibitors had the highest probability of being the most effective regimen with the lowest toxicity .
The combination of daratumumab , lenalidomide , and dexamethasone ranked as the first regimen in terms of activity , efficacy , and tolerability according to the average value between surface under the cumulative ranking curve of PFS , overall survival , ORR , complete response rate , and safety .
This is the first NMA comparing all currently available regimens evaluated in published r and omized trials for the treatment of RRMM , but our results need to be interpreted taking into account differences in their patient population s. Our analysis suggests that IMiDs plus new anti-MM mAb-containing regimens are the most active therapeutic option in RRMM