***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 PURPOSE This phase I study evaluated elotuzumab , lenalidomide , and dexamethasone in patients with relapsed or refractory multiple myeloma ( MM ) . PATIENTS AND METHODS Three cohorts were enrolled and treated with elotuzumab ( 5.0 , 10 , or 20 mg/kg intravenously ) on days 1 , 8 , 15 , and 22 of a 28-day cycle in the first two cycles , and days 1 and 15 of each subsequent cycle ; lenalidomide 25 mg orally [ PO ] on days 1 to 21 ; and dexamethasone 40 mg PO weekly . Dose-limiting toxicities ( DLTs ) were assessed during cycle 1 of each cohort , and clinical responses were evaluated during each cycle . The first five patients received up to six cycles of therapy ; subsequent patients were treated until disease progression . RESULTS Twenty-nine patients with advanced MM and a median of three prior MM therapies were enrolled ; 28 patients were treated , three each in the 5.0-mg/kg and 10-mg/kg cohorts and 22 in the 20-mg/kg cohort . No DLTs were observed up to the maximum proposed dose of 20 mg/kg . The most frequent grade 3 to 4 toxicities were neutropenia ( 36 % ) and thrombocytopenia ( 21 % ) . Two patients experienced a serious infusion reaction ( one grade 4 anaphylactic reaction and one grade 3 stridor ) during the first treatment cycle . Objective responses were obtained in 82 % ( 23 of 28 ) of treated patients . After a median of 16.4 months follow-up , the median time to progression was not reached for patients in the 20-mg/kg cohort who were treated until disease progression . CONCLUSION The combination of elotuzumab , lenalidomide , and low-dose dexamethasone was generally well tolerated and showed encouraging response rates in patients with relapsed or refractory MM Daratumumab , a human CD38 immunoglobulin G1 kappa ( IgG1κ ) monoclonal antibody , has activity as monotherapy in multiple myeloma ( MM ) . This phase 1/2 study investigated daratumumab plus lenalidomide/dexamethasone in refractory and relapsed/refractory MM . Part 1 ( dose escalation ) evaluated 4 daratumumab doses plus lenalidomide ( 25 mg/day orally on days 1 - 21 of each cycle ) and dexamethasone ( 40 mg/week ) . Part 2 ( dose expansion ) evaluated daratumumab at the recommended phase 2 dose ( RP2D ) plus lenalidomide/dexamethasone .  Safety , efficacy , pharmacokinetics , immunogenicity , and accelerated daratumumab infusions were studied . In part 1 ( 13 patients ) , no dose-limiting toxicities were observed , and 16 mg/kg was selected as the R2PD . In part 2 ( 32 patients ) , median time since diagnosis was 3.2 years , with a median of 2 prior therapies ( range , 1 - 3 prior therapies ) , including proteasome inhibitors ( 91 % ) , alkylating agents ( 91 % ) , autologous stem cell transplantation ( 78 % ) , thalidomide ( 44 % ) , and lenalidomide ( 34 % ) ; 22 % of patients were refractory to the last line of therapy . Grade 3 to 4 adverse events ( ≥5 % ) included neutropenia , thrombocytopenia , and anemia . In part 2 , infusion-related reactions ( IRRs ) occurred in 18 patients ( 56 % ) ; most were grade ≤2 ( grade 3 , 6.3 % ) . IRRs predominantly occurred during first infusions and were more common during accelerated infusions . In part 2 ( median follow-up of 15.6 months ) , overall response rate was 81 % , with 8 stringent complete responses ( 25 % ) , 3 complete responses ( 9 % ) , and 9 very good partial responses ( 28 % ) . Eighteen-month progression-free and overall survival rates were 72 % ( 95 % confidence interval , 51.7 - 85.0 ) and 90 % ( 95 % confidence interval , 73.1 - 96.8 ) ,  respectively . Daratumumab plus lenalidomide/dexamethasone result ed in rapid , deep , durable responses . The combination was well tolerated and consistent with the safety profiles observed with lenalidomide/dexamethasone or daratumumab monotherapy . This trial was registered at www . clinical trials.gov as # NCT01615029 BACKGROUND Few effective treatments exist for patients with refractory or relapsed and refractory multiple myeloma not responding to treatment with bortezomib and lenalidomide . Pomalidomide alone has shown limited efficacy in patients with relapsed multiple myeloma , but synergistic effects have been noted when combined with dexamethasone . We compared the efficacy and safety of pomalidomide plus low-dose dexamethasone with high-dose dexamethasone alone in these patients . METHODS This multicentre , open-label , r and omised phase 3 trial was undertaken in Australia , Canada , Europe , Russia , and the USA . Patients were eligible if they had been diagnosed with refractory or relapsed and refractory multiple myeloma , and had failed at least two previous treatments of bortezomib and lenalidomide .  They were assigned in a 2:1 ratio with a vali date d interactive voice and internet response system to either 28 day cycles of pomalidomide ( 4 mg/day on days 1 - 21 , orally ) plus low-dose dexamethasone ( 40 mg/day on days 1 , 8 , 15 , and 22 , orally ) or high-dose dexamethasone ( 40 mg/day on days 1 - 4 , 9 - 12 , and 17 - 20 , orally ) until disease progression or unacceptable toxicity . Stratification factors were age ( ≤75 years vs > 75 years ) , disease population ( refractory vs relapsed and refractory vs bortezomib intolerant ) , and number of previous treatments ( two vs more than two ) . The primary endpoint was progression-free survival ( PFS ) . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT01311687 , and with EudraCT , number 2010 - 019820 - 30 . FINDINGS The accrual for the study has been completed and the analyses are presented . 302 patients were r and omly assigned to receive pomalidomide plus low-dose dexamethasone and 153 high-dose dexamethasone . After a median follow-up of 10·0 months ( IQR 7·2 - 13·2 ) , median PFS with pomalidomide plus low-dose dexamethasone was 4·0 months ( 95 % CI 3·6 - 4·7 ) versus 1·9 months ( 1·9 - 2·2 ) with high-dose dexamethasone ( hazard ratio 0·48 [ 95 % CI 0·39 - 0·60 ] ; p<0·0001 ) . The most common grade 3 - 4 haematological adverse events  in the pomalidomide plus low-dose dexamethasone and high-dose dexamethasone groups were neutropenia ( 143 [ 48 % ] of 300 vs 24 [ 16 % ] of 150 , respectively ) , anaemia ( 99 [ 33 % ] vs 55 [ 37 % ] , respectively ) , and thrombocytopenia ( 67 [ 22 % ] vs 39 [ 26 % ] , respectively ) . Grade 3 - 4 non-haematological adverse events in the pomalidomide plus low-dose dexamethasone and high-dose dexamethasone groups included pneumonia ( 38 [ 13 % ] vs 12 [ 8 % ] , respectively ) , bone pain ( 21 [ 7 % ] vs seven [ 5 % ] , respectively ) , and fatigue ( 16 [ 5 % ] vs nine [ 6 % ] , respectively ) . There were 11 ( 4 % ) treatment-related adverse events leading to death in the pomalidomide plus low-dose dexamethasone group and seven ( 5 % ) in the high-dose dexamethasone group . INTERPRETATION Pomalidomide plus low-dose dexamethasone , an oral regimen , could be considered a new treatment option in patients with refractory or relapsed and refractory multiple myeloma . FUNDING Celgene Corporation 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 
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Additionally , the efficacy of triplet regimens was superior to that of single or doublet regimens .
The same trend was observed in a subgroup analysis of daratumumab and elotuzumab .
Elotuzumab and daratumumab  improved the ORR , at least VGPR , and PFS compared to non-mAb-based regimens .
In a pooled analysis , both mAbs had promising efficacy and safety profiles , particularly in triplet regimens .
The same trend was observed in daratumumab- and elotuzumab-based regimens .
Daratumumab triplet therapy ( daratumumab , lenalidomide , and dexamethasone ) was superior to other triplet regimens for the treatment of RRMM , and daratumumab monotherapy was more effective than either single agent in heavily pretreated MM patients , suggesting CD38 is an effective target for treatment of RRMM .