***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: Despite improvements in st and ard therapy with rituximab , cyclophosphamide , doxorubicin , vincristine and prednisone for patients with untreated , diffuse large B-cell lymphoma , up to 40 % of these patients relapse . Lenalidomide alone or in combination with rituximab has been shown to be active in relapsed/refractory aggressive lymphomas . In this phase I study we determined the maximum tolerated dose of lenalidomide plus rituximab , cyclophosphamide , doxorubicin , vincristine and prednisone in untreated , elderly ( median age 68 years ) patients with diffuse large B-cell lymphoma . Four lenalidomide doses ( 5 , 10 , 15 , and 20 mg/day on days 1–14 ) allocated using the continual re assessment method were planned to be administered for 14 days in combination with each course of rituximab , cyclophosphamide , doxorubicin , vincristine and prednisone for a total of six courses . Seven cohorts of patients ( n=3 in each cohort ) were treated ( total n=21 ) at 10 , 20 , 15 , 15 , 15 , 10 , and 10 mg of lenalidomide . Dose-limiting toxicities occurred in seven patients during the first three courses of treatment . The third dose-level of lenalidomide ( 15 mg/day ) was selected as the maximum tolerated dose , with an estimated probability of dose-limiting toxicities of 0.345 ( 95 % credibility interval 0.164–0.553 ) . Grade 3–4 hematologic adverse events were : neutropenia in 28 % of the courses , thrombocytopenia in 9 % , and anemia in 3 % . Non-hematologic toxicities were moderate : grade 4 increase of creatinine phosphokinase ( n=1 ) , grade 3 cardiac ( n=2 ) , grade 3 neurological ( n=3 ) , and grade 3 gastrointestinal ( n=1 ) . In this phase I study , the overall response rate was 90 % , with 81 % achieving complete remission . This combination regimen appears safe in elderly patients with diffuse large B-cell lymphoma and its efficacy will be assessed in the ongoing phase II trial . This trial was registered at www . clinical trials.gov as NCT00907348 BACKGROUND Cyclophosphamide , doxorubicin , vincristine , and prednisolone ( CHOP ) is used to treat patients with non-Hodgkin lymphoma . Interval decrease from 3 weeks of treatment ( CHOP-21 ) to 2 weeks ( CHOP-14 ) , and addition of rituximab to CHOP-21 ( R-CHOP-21 ) has been shown to improve outcome in elderly patients with diffuse large B-cell lymphoma ( DLBCL ) . This r and omised trial assessed whether six or eight cycles of R-CHOP-14 can improve outcome of these patients compared with six or eight cycles of CHOP-14 . METHODS 1222 elderly patients ( aged 61 - 80 years ) were r and omly assigned to six or eight cycles of CHOP-14 with or without rituximab . Radiotherapy was planned to sites of initial bulky disease with or without extranodal involvement . The primary endpoint was event-free survival ; secondary endpoints were response , progression during treatment , progression-free survival , overall survival , and frequency of toxic effects . Analyses were done by intention to treat . The trial is registered on National Cancer Institute website , number NCT00052936 and as EU-20243 . FINDINGS 3-year event-free survival was 47.2 % after six cycles of CHOP-14 ( 95 % CI 41.2 - 53.3 ) , 53.0 % ( 47.0 - 59.1 ) after eight cycles of CHOP-14 , 66.5 % ( 60.9 - 72.0 ) after six cycles of R-CHOP-14 , and 63.1 % ( 57.4 - 68.8 ) after eight cycles of R-CHOP-14 . Compared with six cycles of CHOP-14 , the improvement in 3-year event-free survival was 5.8 % ( -2.8 - 14.4 ) for eight cycles of CHOP-14 , 19.3 % ( 11.1 - 27.5 ) for six cycles of R-CHOP-14 , and 15.9 % ( 7.6 - 24.2 ) for eight cycles of R-CHOP-14 . 3-year overall survival was 67.7 % ( 62.0 - 73.5 ) for six cycles of CHOP-14 , 66.0 % ( 60.1 - 71.9 ) for eight cycles of CHOP-14 , 78.1 % ( 73.2 - 83.0 ) for six cycles of R-CHOP-14 , and 72.5 % ( 67.1 - 77.9 ) for eight cycles of R-CHOP-14 . Compared with treatment with six cycles of CHOP-14 , overall survival improved by -1.7 % ( -10.0 - 6.6 ) after eight cycles of CHOP-14 , 10.4 % ( 2.8 - 18.0 ) after six cycles of R-CHOP-14 , and 4.8 % ( -3.1 - 12.7 ) after eight cycles of R-CHOP-14 . In a multivariate analysis that used six cycles of CHOP-14 without rituximab as the reference , and adjusting for known prognostic factors , all three intensified regimens improved 3-year event-free survival ( eight cycles of CHOP-14 : RR [ relative risk ] 0.76 [ 0.60 - 0.95 ] , p=0.0172 ; six cycles of R-CHOP-14 : RR 0.51 [ 0.40 - 0.65 ] , p<0.0001 ; eight cycles of R-CHOP-14 : RR 0.54 [ 0.43 - 0.69 ] , p<0.0001 ) . Progression-free survival improved after six cycles of R-CHOP-14 ( RR 0.50 [ 0.38 - 0.67 ] , p<0.0001 ) , and eight cycles of R-CHOP-14 ( RR 0.59 [ 0.45 - 0.77 ] , p=0.0001 ) . Overall survival improved only after six cycles of R-CHOP-14 ( RR 0.63 [ 0.46 - 0.85 ] , p=0.0031 ) . In patients with a partial response after four cycles of chemotherapy , eight cycles were not better than six cycles . INTERPRETATION Six cycles of R-CHOP-14 significantly improved event-free , progression-free , and overall survival over six cycles of CHOP-14 treatment . Response-adapted addition of chemotherapy beyond six cycles , though widely practice d , is not justified . Of the four regimens assessed in this study , six cycles of R-CHOP-14 is the preferred treatment for elderly patients , with which other approaches should be compared Lenalidomide – rituximab therapy is effective in grade 1–2 follicular and mantle cell lymphoma , but its efficacy in diffuse large B-cell lymphoma ( DLBCL ) , transformed large cell lymphoma ( TL ) and grade 3 follicular lymphoma ( FLG3 ) is unknown . In this phase II trial , 45 patients with relapsed or refractory DLBCL ( n=32 ) , TL ( n=9 ) or FLG3 ( n=4 ) who had received 1–4 prior lines of treatment were given 20 mg oral lenalidomide on days 1–21 of each 28-day cycle , and intravenous rituximab ( 375 mg/m2 ) weekly during cycle 1 . Grade 3/4 hematological toxicities included neutropenia ( 53 % ) , lymphopenia ( 40 % ) , thrombocytopenia ( 33 % ) , leukopenia ( 27 % ) and anemia ( 18 % ) , with a median follow-up time of 29.1 months ( range 14.7–52.0 months ) . Overall response ( OR ) rate was 33 % ; median response duration was 10.2 months . Median progression-free survival ( PFS ) and overall survival ( OS ) were 3.7 and 10.7 months , respectively . Nine of the 15 responding patients ( three partial response ( PR ) , six complete response ( CR ) ) proceeded with stem cell transplantation ( SCT ) and were censored at the time of transplantation . When data were analyzed without censoring , median PFS remained 3.7 months and response duration increased to 30.9 months . Rituximab plus oral lenalidomide is well tolerated and effective for patients with relapsed/refractory DLBCL and TL . SCT after lenalidomide – rituximab is associated with prolonged response duration Relapsed/refractory diffuse large B‐cell lymphoma ( DLBCL ) is associated with a poor prognosis . Outcomes are particularly poor following immunochemotherapy failure or relapse within 12 months of induction . We conducted a Phase I/II trial of lenalidomide plus RICE ( rituximab , ifosfamide , carboplatin , and etoposide ) ( RICER ) as a salvage regimen for first‐relapse or primary refractory DLBCL .  Dose‐escalated lenalidomide was combined with RICE every 14 d. After three cycles of RICER , patients with chemosensitive disease underwent stem cell collection and consolidation with BEAM [ BCNU ( carmustine ) , etoposide , cytarabine , melphalan ] followed by autologous stem cell transplantation ( autoSCT ) . Patients who recovered from autoSCT toxicities within 90 d initiated maintenance treatment with lenalidomide 25 mg daily for 21 d every 28 d for 12 months . No dose‐limiting or unexpected toxicities occurred with lenalidomide 25 mg plus RICE . Grade 3/4 haematological toxicities resolved appropriately , and planned dose density and dose intensity of RICER were preserved . No lenalidomide or RICE dose reductions were required in any of the three cycles . After two cycles of RICER , nine of 15 patients ( 60 % ) achieved a complete response , and two achieved a partial response ( 13 % ) . Combining lenalidomide with RICE is feasible , and results in promising response rates ( particularly complete response rates ) in high‐risk DLBCL patients BACKGROUND Lenalidomide is an immunomodulatory agent with antitumor activity in B-cell malignancies . This phase II trial aim ed to demonstrate the safety and efficacy of lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma ( DLBCL ) , mantle cell lymphoma ( MCL ) , follicular grade 3 lymphoma ( FL-III ) , or transformed lymphoma ( TL ) . METHODS Patients received oral lenalidomide 25 mg on days 1 - 21 every 28 days as tolerated or until progression . The primary end point was overall response rate ( ORR ) . RESULTS Two hundred and seventeen patients enrolled and received lenalidomide .  The ORR was 35 % ( 77/217 ) , with 13 % ( 29/217 ) complete remission ( CR ) , 22 % ( 48/217 ) partial remission , and 21 % ( 45/217 ) with stable disease . The ORR for DLBCL was 28 % ( 30/108 ) , 42 % ( 24/57 ) for MCL , 42 % ( 8/19 ) for FL-III , and 45 % ( 15/33 ) for TL . Median progression-free survival for all 217 patients was 3.7 months [ 95 % confidence interval ( CI ) 2.7 - 5.1 ] . For 77 responders , the median response duration lasted 10.6 months ( 95 % CI 7.0-NR ) . Median response duration was not reached in 29 patients who achieved a CR and in responding patients with FL-III or MCL . The most common adverse event was myelosuppression with grade 4 neutropenia and thrombocytopenia in 17 % and 6 % , respectively . CONCLUSION Lenalidomide is well tolerated and produces durable responses in patients with relapsed or refractory aggressive non-Hodgkin 's lymphoma BACKGROUND Up to 40 % of elderly patients with untreated diffuse large B-cell lymphoma ( DLBCL ) given a regimen of rituximab , cyclophosphamide , doxorubicin , vincristine , and prednisolone every 21 days ( R-CHOP21 ) relapse or develop refractory disease . Lenalidomide has high activity in relapsed or refractory aggressive B-cell lymphomas . In phase 2 of the REAL07 trial , we aim ed to establish the safety and efficacy of the combination of lenalidomide and R-CHOP21 in elderly patients with untreated DLBCL . 
    Output:
    
More importantly , after lenalidomide treatment , the patients with non-GCB DLBCL did not show significantly worse progression-free survival ( PFS ) and overall survival ( OS ) compared with GCB subtype .
Lenalidomide as treatments for DLBCL patients , non-GCB DLBCL patients did not show significantly worse prognosis compared with GCB DLBCL