***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 patients with multiple myeloma ( MM ) , risk stratification by chromosomal abnormalities may enable a more rational selection of therapeutic approaches . In the present study , we analyzed the prognostic value of 12 chromosomal abnormalities in a series of 354 MM patients treated within the HOVON-65/GMMG-HD4 trial . Because of the 2-arm design of the study , we were able to analyze the effect of a bortezomib-based treatment before and after autologous stem cell transplantation ( arm B ) compared with st and ard treatment without bortezomib ( arm A ) . For allanalyzed chromosomal aberrations , progression-free survival ( PFS ) and overall survival ( OS ) were at least equal or superior in the bortezomib arm compared with the st and ard arm . Strikingly , patients with del(17p13 ) benefited the most from the bortezomib-containing treatment : the median PFS in arm A was 12.0 months and in arm B it was 26.2 months ( P = .024 ) ; the 3 year-OS for arm A was 17 % and for arm B it was 69 % ( P = .028 ) . After multivariate analysis , del(17p13 ) was an independent predictor for PFS ( P < .0001 ) and OS ( P < .0001 ) in arm A , whereas no statistically significant effect on PFS ( P = .28 ) or OS ( P = .12 ) was seen in arm B. In conclusion , the adverse impact of del(17p13 ) on PFS and OS could be significantly reduced by bortezomib-based treatment , suggesting that long-term administration of bortezomib should be recommended for patients carrying del(17p13 ) BACKGROUND Thalidomide plus dexamethasone ( TD ) is a st and ard induction therapy for myeloma . We aim ed to assess the efficacy and safety of addition of bortezomib to TD ( VTD ) versus TD alone as induction therapy before , and consolidation therapy after , double autologous stem-cell transplantation in newly diagnosed multiple myeloma . METHODS Patients ( aged 18 - 65 years ) with previously untreated symptomatic myeloma were enrolled from 73 sites in Italy between May , 2006 , and April , 2008 , and data collection continued until June 30 , 2010 . Patients were r and omly allocated ( 1:1 ratio ) by a web-based system to receive three 21-day cycles of thalidomide ( 100 mg daily for the first 14 days and 200 mg daily thereafter ) plus dexamethasone ( 40 mg daily on 8 of the first 12 days , but not consecutively ; total of 320 mg per cycle ) , either alone or with bortezomib ( 1·3 mg/m(2 ) on days 1 , 4 , 8 , and 11 ) . The r and omisation sequence was computer generated by the study coordinating team and was stratified by disease stage . After double autologous stem-cell transplantation , patients received two 35-day cycles of their assigned drug regimen , VTD or TD , as consolidation therapy . The primary endpoint was the rate of complete or near complete response to induction therapy . Analysis was by intention to treat . Patients and treating physicians were not masked to treatment allocation . This study is still underway but is not recruiting participants , and is registered with Clinical Trials.gov , number NCT01134484 , and with EudraCT , number 2005 - 003723 - 39 . FINDINGS 480 patients were enrolled and r and omly assigned to receive VTD ( n=241 patients ) or TD ( n=239 ) . Six patients withdrew consent before start of treatment , and 236 on VTD and 238 on TD were included in the intention-to-treat analysis . After induction therapy , complete or near complete response was achieved in 73 patients ( 31 % , 95 % CI 25·0 - 36·8 ) receiving VTD , and 27 ( 11 % , 7·3 - 15·4 ) on TD ( p<0·0001 ) . Grade 3 or 4 adverse events were recorded in a significantly higher number of patients on VTD ( n=132 , 56 % ) than in those on TD ( n=79 , 33 % ; p<0·0001 ) , with a higher occurrence of peripheral neuropathy in patients on VTD ( n=23 , 10 % ) than in those on TD ( n=5 , 2 % ; p=0·0004 ) . Resolution or improvement of severe peripheral neuropathy was recorded in 18 of 23 patients on VTD , and in three of five patients on TD . INTERPRETATION VTD induction therapy before double autologous stem-cell transplantation significantly improves rate of complete or near complete response , and represents a new st and ard of care for patients with multiple myeloma who are eligible for transplant . FUNDING Seràgnoli Institute of Haematology at the University of Bologna , Bologna , Italy The role of maintenance therapy in multiple myeloma is controversial . Recent studies have shown an improvement in both progression-free and overall survival for patients receiving maintenance treatment with a combination of interferon and glucocorticoids  , compared with interferon alone . The role of glucocorticoids alone as maintenance therapy has not been previously addressed . We compared alternate-day , oral prednisone at 2 different dose levels ( 10 mg versus 50 mg ) for remission maintenance among previously untreated myeloma patients following a response to induction with st and ard-dose vincristine , doxorubicin , and dexamethasone with prednisone ( VAD-P ) or VAD-P plus quinine ( VAD-P/Q ) . There were 250 eligible patients registered on Southwest Oncology Group study 9210 and r and omized to receive VAD-P or VAD-P/Q.  There were 125 patients achieving at least a 25 % tumor reduction following induction therapy who were r and omized to either physiologic ( 10 mg ) or pharmacologic ( 50 mg ) doses of alternate-day , oral prednisone until disease progression . At the time of study entry , patient characteristics were similar in VAD-P and VAD-P/Q patients and in the 2 arms r and omized to maintenance therapy . After a median follow-up of 53 months , there was no difference in either progression-free or overall survival between the 2 induction regimens . However , from the time of maintenance r and omization , both progression-free ( 14 versus 5 months ; P = .003 ) and overall survival ( 37 versus 26 months ; P = .05 ) were significantly improved in patients receiving 50 mg as compared with 10 mg alternate-day prednisone . There was no difference in treatment-related adverse events between the groups . Thus , 50 mg , oral , alternate-day prednisone is effective maintenance treatment for multiple myeloma patients who achieve a response to induction chemotherapy . ( Blood . 2002;99:3163 - 3168 Background and Objectives The proteasome inhibitor bortezomib is approved for the treatment of multiple myeloma ( MM ) and , in the US , for the treatment of mantle cell lymphoma following at least one prior therapy ; the recommended dose and schedule is 1.3 mg/m2 on days 1 , 4 , 8 and 11 of 21-day cycles , and the approved routes of administration in the US prescribing information are by intravenous and , following a recent up date , subcutaneous injection . Findings from a phase III study demonstrated that subcutaneous administration of bortezomib , using the same dose and schedule , result ed in similar efficacy with an improved systemic safety profile ( including significantly lower rates of peripheral neuropathy ) versus intravenous bortezomib in patients with relapsed MM . The objectives of this report were to present a comprehensive analysis of the pharmacokinetics and pharmacodynamics of subcutaneous versus intravenous bortezomib  , and to evaluate the impact of the subcutaneous administration site , subcutaneous injection concentration and demographic characteristics on bortezomib pharmacokinetics and pharmacodynamics . Patients and Methods Data were analysed from the pharmacokinetic sub study of the r and omized phase III MMY-3021 study and the phase I CAN-1004 study of subcutaneous versus intravenous bortezomib  in patients aged ≥18 ( MMY-3021 ) or ≤75 ( CAN-1004 ) years with symptomatic relapsed or refractory MM after 1–3 ( MMY-3021 ) or ≥1 ( CAN-1004 ) prior therapies . Patients received up to eight 21-day cycles of subcutaneous or intravenous bortezomib 1.3 mg/m2 on days 1 , 4 , 8 and 11 . Pharmacokinetic and pharmacodynamic ( 20S proteasome inhibition ) parameters  of bortezomib following subcutaneous or intravenous administration were evaluated on day 11 , cycle 1 .  Results Bortezomib systemic exposure was equivalent with subcutaneous versus intravenous administration in MMY-3021 [ mean area under the plasma concentration – time curve from time zero to the last quantifiable timepoint ( AUClast ) : 155 vs. 151 ng·h/mL ; geometric mean ratio 0.992 ( 90 % CI 80.18 , 122.80 ) ] and comparable in CAN-1004 ( mean AUClast : 195 vs. 241 ng·h/mL ) ; maximum ( peak ) plasma drug concentration ( Cmax ) was lower with subcutaneous administration in both MMY-3021 ( mean 20.4 vs. 223 ng/mL ) and CAN-1004 ( mean 22.5 vs. 162 ng/mL ) , and time to Cmax ( tmax ) was longer with subcutaneous administration in both studies ( median 30 vs. 2 min ) . Blood 20S proteasome inhibition pharmacodynamic parameters were also similar with subcutaneous versus intravenous bortezomib : mean maximum effect ( Emax ) was 63.7 versus 69.3 % in MMY-3021 and 57.0 versus 68.8 % in CAN-1004 , and mean area under the effect – time curve from time zero to 72 h was 1,714 versus 1,383 % · h in MMY-3021 and 1,619 versus 1,283 % · h in CAN-1004 . Time to Emax was longer with subcutaneous administration in MMY-3021 ( median 120 vs. 5 min ) and CAN-1004 ( median 120 vs. 3 min ) . Concentration of the subcutaneous injected solution had no appreciable effect on pharmacokinetic or pharmacodynamic parameters . There were no apparent differences in bortezomib pharmacokinetic and pharmacodynamic parameters between subcutaneous administration in the thigh or abdomen . There were also no apparent differences in bortezomib exposure related to body mass index , body surface area or age . ConclusionS ubcutaneous administration results in equivalent bortezomib plasma exposure to intravenous administration , together with comparable blood 20S proteasome inhibition pharmacodynamic effects . These findings , together with the non-inferior efficacy of subcutaneous versus intravenous bortezomib demonstrated in MMY-3021 , support the use of bortezomib via the subcutaneous route across the setting s of clinical use in which the safety and efficacy of intravenous bortezomib has been established 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 
    Output:
    
The corresponding cumulative meta-analyses of the rates of overall response rate , complete response and near complete response , and grade s 3 and 4 peripheral neuropathy supported the superiority of bortezomib-based maintenance therapy over consolidation therapy .
Bortezomib-based therapy after autologous stem cell transplantation , with tolerable AEs , could obviously improve the response as well as the outcome of multiple myeloma patients , particularly when bortezomib was administered as maintenance therapy