***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: This study evaluated the cost effectiveness of  bortezomib  in relapsed , refractory myeloma , relative to best supportive care ( BSC ) and thalidomide . Data were derived from the phase 2 pivotal study of bortezomib  , a Delphi panel of six myeloma thought leaders , and published literature . Objective assumptions regarding treatment choices and consequences ( response and complications ) , and actual cost data were used . Bortezomib was found to be cost effective relative to BSC and thalidomide . Sensitivity analyses demonstrated the robustness of the results . These data suggest that bortezomib provides a cost-effective treatment option and the best value ( in terms of cost/life-yr gained ) among the currently available therapeutic options for relapsed , refractory myeloma BACKGROUND In multiple myeloma , combination chemotherapy with melphalan plus prednisone is still regarded as the st and ard of care in elderly patients . We assessed whether the addition of thalidomide to this combination , or reduced-intensity stem cell transplantation , would improve survival . METHODS Between May 22 , 2000 , and Aug 8 , 2005 , 447 previously untreated patients with multiple myeloma , who were aged between 65 and 75 years , were r and omly assigned to receive either melphalan and prednisone ( MP ; n=196 ) , melphalan and prednisone plus thalidomide ( MPT ; n=125 ) , or reduced-intensity stem cell transplantation using melphalan 100 mg/m2 ( MEL100 ; n=126 ) . The primary endpoint was overall survival . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00367185 . FINDINGS After a median follow-up of 51.5 months ( IQR 34.4 - 63.2 ) , median overall survival times were 33.2 months ( 13.8 - 54.8 ) for MP , 51.6 months ( 26.6-not reached ) for MPT , and 38.3 months ( 13.0 - 61.6 ) for MEL100 . The MPT regimen was associated with a significantly better overall survival than was the MP regimen ( hazard ratio 0.59 , 95 % CI 0.46 - 0.81 , p=0.0006 ) or MEL100 regimen ( 0.69 , 0.49 - 0.96 , p=0.027 ) . No difference was seen for MEL100 versus MP ( 0.86 , 0.65 - 1.15 , p=0.32 ) . INTERPRETATION The results of our trial provide strong evidence to indicate that the use of thalidomide in combination with melphalan and prednisone should , at present , be the reference treatment for previously untreated elderly patients with multiple myeloma BACKGROUND Since 1960 , oral melphalan and prednisone ( MP ) has been regarded as the st and ard of care in elderly multiple myeloma patients . This multicentre r and omised trial compared oral MP plus thalidomide ( MPT ) with MP alone in patients aged 60 - 85 years . METHODS Patients with newly diagnosed multiple myeloma were r and omly assigned to receive oral MP for six 4-week cycles plus thalidomide ( n=129 ; 100 mg per day continuously until any sign of relapse or progressive disease ) or MP alone ( n=126 ) . Analysis was intention-to-treat . This study is registered at , number NCT00232934 . RESULTS Patients treated with thalidomide had higher response rates and longer event-free survival ( primary endpoints ) than patients who were not . Combined complete or partial response rates were 76.0 % for MPT and 47.6 % for MP alone ( absolute difference 28.3 % , 95 % CI 16.5 - 39.1 ) , and the near-complete or complete response rates were 27.9 % and 7.2 % , respectively . 2-year event-free survival rates were 54 % for MPT and 27 % for MP ( hazard ratio [ HR ] for MPT 0.51 , 95 % CI 0.35 - 0.75 , p=0.0006 ) . 3-year survival rates were 80 % for MPT and 64 % for MP ( HR for MPT 0.68 , 95 % CI 0.38 - 1.22 , p=0.19 ) . Rates of grade 3 or 4 adverse events were 48 % in MPT patients and 25 % in MP patients ( p=0.0002 ) . Introduction of enoxaparin prophylaxis reduced rate of thromboembolism from 20 % to 3 % ( p=0.005 ) . CONCLUSION Oral MPT is an effective first-line treatment for elderly patients with multiple myeloma . Anticoagulant prophylaxis reduces frequency of thrombosis . Longer follow-up is needed to assess effect on overall survival The Spanish Myeloma Group conducted a trial to compare bortezomib/thalidomide/dexamethasone ( VTD ) versus thalidomide/dexamethasone ( TD ) versus vincristine , BCNU , melphalan , cyclophosphamide , prednisone/vincristine , BCNU , doxorubicin , dexamethasone/bortezomib ( V BMC P/VBAD/B ) in patients aged 65 years or younger with multiple myeloma . The primary endpoint was complete response ( CR ) rate postinduction and post-autologous stem cell transplantation ( ASCT ) . Three hundred eighty-six patients were allocated to VTD ( 130 ) , TD ( 127 ) , or V BMC P/VBAD/B ( 129 ) . The CR rate was significantly higher with VTD than with TD ( 35 % vs 14 % , P = .001 ) or with V BMC P/VBAD/B ( 35 % vs 21 % , P = .01 ) . The median progression-free survival ( PFS ) was significantly longer with VTD ( 56.2 vs 28.2 vs 35.5 months , P = .01 ) . In an intention-to-treat analysis , the post-ASCT CR rate was higher with VTD than with TD ( 46 % vs 24 % , P = .004 ) or with V BMC P/VBAD/B ( 46 % vs 38 % , P = .1 ) . Patients with high-risk cytogenetics  had a shorter PFS and overall survival in the overall series and in all treatment groups . In conclusion , VTD result ed in a higher pre- and posttransplantation CR rate and in a significantly longer PFS although it was not able to overcome the poor prognosis of high-risk cytogenetics . Our results support the use of VTD as a highly effective induction regimen prior to ASCT . The study was registered with http://www . clinical trials.gov ( NCT00461747 ) and Eudra CT ( no. 2005 - 001110 - 41 ) As part of the r and omized MRC Myeloma IX trial , we compared an attenuated regimen of cyclophosphamide , thalidomide , and dexamethasone ( CTDa ; n = 426 ) with melphalan and prednisolone ( MP ; n = 423 ) in patients with newly diagnosed multiple myeloma ineligible for autologous stem-cell transplantation . The primary endpoints were overall response rate , progression-free survival , and overall survival ( OS ) . The overall response rate was significantly higher with CTDa than MP ( 63.8 % vs 32.6 % ; P < .0001 ) , primarily because of increases in the rate of complete responses ( 13.1 % vs 2.4 % ) and very good partial responses ( 16.9 % vs 1.7 % ) . Progression-free survival and OS were similar between groups . In this population , OS correlated with the depth of response ( P < .0001 ) and favorable interphase fluorescence in situ hybridization profile ( P < .001 ) . CTDa was associated with higher rates of thromboembolic events , constipation , infection , and neuropathy than MP . In elderly patients with newly diagnosed multiple myeloma ( median age , 73 years ) , CTDa produced higher response rates than MP but was not associated with improved survival outcomes . We highlight the importance of cytogenetic profiling at diagnosis and effective management of adverse events . This trial was registered at International St and ard R and omized Controlled Trials Number as # 68454111 Background Thalidomide is active in multiple myeloma and is associated with minimal myelosuppression , making it a good c and i date for induction therapy prior to high-dose therapy with autologous stem-cell transplantation . Design and Methods Oral cyclophosphamide , thalidomide , and dexamethasone was compared with infusional cyclophosphamide , vincristine , doxorubicin , and dexamethasone in patients with newly diagnosed multiple myeloma . Results The post-induction overall response rate ( ≥ partial response ) for the intent-to-treat population was significantly higher with cyclophosphamide-thalidomide-dexamethasone ( n=555 ) versus cyclophosphamide-vincristine-doxorubicin-dexamethasone ( n=556 ) ; 82.5 % versus 71.2 % ; odds ratio 1.91 ; 95 % confidence interval 1.44–2.55 ; P<0.0001 . The complete response rates were 13.0 % with cyclophosphamide-thalidomide-dexamethasone and 8.1 % with cyclophos-phamide-vincristine-doxorubicin-dexamethasone ( P=0.0083 ) , with this differential response being maintained in patients who received autologous stem-cell transplantation ( post-transplant complete response 50.0 % versus 37.2 % , respectively ; P=0.00052 ) . Cyclophosphamide-thalidomide-dexamethasone was non-inferior to cyclophosphamide-vincristine-doxorubicin-dexamethasone  for progression-free and overall survival , and there was a trend toward a late survival benefit with cyclophosphamide-thalidomide-dexamethasone in responders . A trend toward an overall survival  advantage for cyclophosphamide-thalidomide-dexamethasone over cyclophosphamide-vincristine-doxorubicin-dexamethasone was also observed in a subgroup of patients with favorable interphase fluorescence in situ hybridization . Compared with cyclophosphamide-vincristine-doxorubicin-dexamethasone , cyclophosphamide-thalidomide-dexamethasone was associated with more constipation and somnolence , but a lower incidence of cytopenias . Conclusions The cyclophosphamide-thalidomide-dexamethasone regimen showed improved response rates and was not inferior in terms of survival outcomes to the st and ard infusional regimen of cyclophosphamide-vincristine-doxorubicin-dexamethasone . Based on its oral administration and the reduced incidence of infection and cytopenia , cyclophosphamide-thalidomide-dexa-methasone may be considered an effective induction therapy option for patients with newly diagnosed multiple myeloma . ( IS RCT N : 68454111 BACKGROUND Lenalidomide has tumoricidal and immunomodulatory activity against multiple myeloma . This double-blind , multicenter , r and omized study compared melphalan-prednisone-lenalidomide induction followed by lenalidomide maintenance ( MPR-R ) with melphalan-prednisone-lenalidomide ( MPR ) or melphalan-prednisone ( MP ) followed by placebo in patients 65 years of age or older with newly diagnosed multiple myeloma . METHODS We r and omly assigned patients who were ineligible for transplantation to receive  MPR-R  ( nine 4-week cycles of MPR followed by lenalidomide maintenance therapy until a relapse or disease progression occurred [ 152 patients ] ) or to receive MPR ( 153 patients ) or MP ( 154 patients ) without maintenance therapy . The primary end point was progression-free survival . RESULTS The median follow-up period was 30 months . The median progression-free survival was significantly longer with MPR-R ( 31 months ) than with MPR ( 14 months ; hazard ratio , 0.49 ; P<0.001 ) or MP ( 13 months ; hazard ratio , 0.40 ; P<0.001 ) . Response rates were superior with MPR-R and MPR ( 77 % and 68 % , respectively , vs. 50 % with MP ; P<0.001 and P=0.002 , respectively , for the comparison with MP ) . The progression-free survival benefit associated with MPR-R was noted in patients 65 to 75 years of age but not in those older than 75 years of age ( P=0.001 for treatment-by-age interaction ) . After induction therapy , a l and mark analysis showed a 66 % reduction in the rate of progression with MPR-R ( hazard ratio for the comparison with MPR , 0.34 ; P<0.0 
    Output:
    
Published CEAs suggested that BTZ or BTZ-containing regimens were cost-effective when compared to most non-BTZ treatments for MM .