***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: Pomalidomide and low-dose dexamethasone ( PomDex ) is st and ard treatment of lenalidomide refractory myeloma patients who have received > 2 prior therapies . We aim ed to assess the safety and efficacy of the addition of oral weekly cyclophosphamide to st and ard PomDex . We first performed a dose escalation phase 1 study to determine the recommended phase 2 dose of cyclophosphamide in combination with PomDex ( arm A ) . A r and omized , multicenter phase 2 study followed , enrolling patients with lenalidomide refractory myeloma . Patients were r and omized ( 1:1 ) to receive pomalidomide 4 mg on days 1 to 21 of a 28-day cycle in combination with weekly dexamethasone ( arm B ) or pomalidomide , dexamethasone , and cyclophosphamide ( PomCyDex ) 400 mg orally on days 1 , 8 , and 15 ( arm C ) . The primary end point was overall response rate ( ORR ) . Eighty patients were enrolled ( 10 in phase 1 and 70 r and omized in phase 2 : 36 to arm B and 34 to arm C ) . The ORR was 38.9 % ( 95 % confidence interval [ CI ] , 23 - 54.8 % ) and 64.7 % ( 95 % CI , 48.6 - 80.8 % ) for arms B and C , respectively ( P = .035 ) . As of June 2015 , 62 of the 70 r and omized patients had progressed . The median progression-free survival ( PFS ) was 4.4 ( 95 % CI , 2.3 - 5.7 ) and 9.5 months ( 95 % CI , 4.6 - 14 ) for arms B and C , respectively ( P = .106 ) . Toxicity was predominantly hematologic in nature but was not statistically higher in arm C. The combination of PomCyDex results in a superior ORR and PFS  compared with PomDex in patients with lenalidomide refractory multiple myeloma . The trial was registered at www . clinical trials.gov as # NCT01432600 Bortezomib frequently produces severe treatment-related peripheral neuropathy ( PN ) in Waldenström 's macroglobulinemia ( WM ) .  Carfilzomib is a neuropathy-sparing proteasome inhibitor . We examined carfilzomib , rituximab , and dexamethasone ( CaRD ) in symptomatic WM patients naïve to bortezomib and rituximab . Protocol therapy consisted of intravenous carfilzomib , 20 mg/m2 ( cycle 1 ) and 36 mg/m(2 ) ( cycles 2 - 6 ) , with intravenous dexamethasone , 20 mg , on days 1 , 2 , 8 , and 9 , and rituximab , 375 mg/m(2 ) , on days 2 and 9 every 21 days . Maintenance therapy followed 8 weeks later with intravenous carfilzomib , 36 mg/m(2 ) , and intravenous dexamethasone , 20 mg , on days 1 and 2 , and rituximab , 375 mg/m(2 ) , on day 2 every 8 weeks for 8 cycles . Overall response rate was 87.1 % ( 1 complete response , 10 very good partial responses , 10 partial responses , and 6 minimal responses ) and was not impacted by MYD88(L265P ) or CXCR4(WHIM ) mutation status . With a median follow-up of 15.4 months , 20 patients remain progression free . Grade ≥2 toxicities included asymptomatic hyperlipasemia ( 41.9 % ) , reversible neutropenia ( 12.9 % ) , and cardiomyopathy in 1 patient ( 3.2 % ) with multiple risk factors , and PN in 1 patient ( 3.2 % ) which was grade 2 . Declines in serum IgA and IgG were common . CaRD offers a neuropathy-sparing approach for proteasome inhibitor-based therapy in WM . This trial is registered at www . clinical trials.gov as # NCT01470196 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 The combination of pomalidomide and low-dose dexamethasone ( Pom-Dex ) can be safely administered to patients with end-stage relapsed/refractory multiple myeloma ( RRMM ) . However , we observed a shorter median progression-free survival ( PFS ) and overall survival ( OS ) in these patients when characterized with adverse cytogenetics ( deletion 17p and translocation [ 4;14 ] ) in the Intergroupe Francophone Myélome ( IFM ) 2009 - 02 trial . We then sought to determine whether MM with adverse cytogenetics would benefit more from Pom-Dex if exposed earlier in the multicenter IFM 2010 - 02 trial . The intention-to-treat population included 50 patients , with a median age of 63 years ( 38 % were ≥65 years ) . Interestingly , there was a striking difference in time to progression ( TTP ) , duration of response , and overall response rate ( ORR ) according to the presence of del(17p ) compared with t(4;14 ) ( TTP , 7.3 vs 2.8 months ; duration of response , 8.3 vs 2.4 months ; and ORR , 32 % vs 15 % ) . OS was prolonged after Pom-Dex , particularly in t(4;14 ) , given the short TTP , suggesting that patients were rescued at relapse with further lines of therapy . Pom-Dex , a doublet immunomodulatory drug-based regimen , is active and well tolerated in adverse cytogenetic patients with early RRMM , particularly in those with del(17p ) , who are characterized by a high and rapid development of a refractoriness state and known for their poor prognosis . Future studies will determine the underlying mechanisms of Pom-Dex activity in del(17p ) . This trial is registered at www . clinical trials.gov as # NCT01745640 This multicenter , open-label , r and omized phase 2 study assessed the efficacy and safety of pomalidomide ( POM ) with/without low-dose dexamethasone ( LoDEX ) in patients with relapsed/refractory multiple myeloma ( RRMM ) . Patients who had received ≥2 prior therapies ( including lenalidomide [ LEN ] and bortezomib [ BORT ] ) and had progressed within 60 days of their last therapy were r and omized to POM ( 4 mg/day on days 1 - 21 of each 28-day cycle ) with/without LoDEX ( 40 mg/week ) . The primary end point was progression-free survival ( PFS ) . In total , 221 patients ( median 5 prior therapies , range 1 - 13 )  received POM+LoDEX ( n = 113 ) or POM ( n = 108 ) . With a median follow-up of 14.2 months , median PFS was 4.2 and 2.7 months ( hazard ratio = 0.68 , P = .003 ) , overall response rates ( ORRs ) were 33 % and 18 % ( P = .013 ) , median response duration was 8.3 and 10.7 months , and median overall survival ( OS ) was 16.5 and 13.6 months , respectively . Refractoriness to LEN , or resistance to both LEN and BORT , did not affect outcomes with POM+LoDEX ( median PFS 3.8 months for both ; ORRs 30 % and 31 % ; and median OS 16 and 13.4 months ) . Grade 3 - 4 neutropenia occurred in 41 % ( POM+LoDEX ) and 48 % ( POM ) ; no grade 3 - 4 peripheral neuropathy was reported . POM+LoDEX  was effective and generally well tolerated and provides an important new treatment option for RRMM patients who have received multiple prior therapies . This trial was registered at www . clinical trials.gov as # NCT00833833 The combination of pomalidomide and dexamethasone can be safely administered to patients with multiple myeloma ( MM ) and has significant efficacy , although the optimal regimen remains to be determined . Patients with MM whose disease progressed after multiple lines of therapy have limited treatment options . We design ed a multicenter , phase 2 r and omized study assessing two different dose regimens of pomalidomide and dexamethasone in advanced MM . Treatment response was assessed central ly . Pomalidomide ( 4 mg ) was given orally on days 1 to 21 ( arm 21/28 ) or continuously ( arm 28/28 ) over a 28-day cycle , plus dexamethasone given weekly . Eighty-four patients ( 43 , arm 21/28 and 41 , arm 28/28 ) were r and omized . The median number of prior lines was 5 . Overall response rate was 35 % ( arm 21/28 ) and 34 % ( arm 28/28 ) , independent of the number of prior lines and level of refractoriness . Median duration of response , time to 
    Output:
    
Pomalidomide was generally well tolerated by patients reported in the studies .