scholarly journals ROBUST: A Phase III Study of Lenalidomide Plus R-CHOP Versus Placebo Plus R-CHOP in Previously Untreated Patients With ABC-Type Diffuse Large B-Cell Lymphoma

2021 ◽  
pp. JCO.20.01366
Author(s):  
Grzegorz S. Nowakowski ◽  
Annalisa Chiappella ◽  
Randy D. Gascoyne ◽  
David W. Scott ◽  
Qingyuan Zhang ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
Bulky Disease ◽  
End Point ◽  
Large B Cell Lymphoma ◽  
Phase Iii Study ◽  
Large B Cell

PURPOSE Patients with the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) historically showed inferior survival with standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Phase II studies demonstrated that adding the immunomodulatory agent lenalidomide to R-CHOP improved outcomes in ABC-type DLBCL. The goal of the global, phase III ROBUST study was to compare lenalidomide plus R-CHOP (R2-CHOP) with placebo/R-CHOP in previously untreated, ABC-type DLBCL. METHODS Histology and cell-of-origin type were prospectively analyzed by central pathology prior to random assignment and study treatment. Patients with ABC-DLBCL received lenalidomide oral 15 mg/d, days 1-14/21 plus standard R-CHOP21 versus placebo/R-CHOP21 for six cycles. The primary end point was progression-free survival (PFS) per independent central radiology review. RESULTS A total of 570 patients with ABC-DLBCL (n = 285 per arm) were stratified by International Prognostic Index score, age, and bulky disease, and randomly assigned to R2-CHOP or placebo/R-CHOP. Baseline demographics were similar between arms. Most patients completed six cycles of treatment: 74% R2-CHOP and 84% placebo/R-CHOP. The most common grade 3/4 adverse events for R2-CHOP versus placebo/R-CHOP were neutropenia (60% v 48%), anemia (22% v 14%), thrombocytopenia (17% v 11%), and leukopenia (14% v 15%). The primary end point of PFS was not met, with a hazard ratio of 0.85 (95% CI, 0.63 to 1.14) and P = .29; median PFS has not been reached for either arm. PFS trends favoring R2-CHOP over placebo/R-CHOP were seen in patients with higher-risk disease. CONCLUSION ROBUST is the first DLBCL phase III study to integrate biomarker-driven identification of eligible ABC patients. Although the ROBUST trial did not meet the primary end point of PFS in all patients, the safety profile of R2-CHOP was consistent with individual treatments with no new safety signals.

Lenalidomide Maintenance Compared With Placebo in Responding Elderly Patients With Diffuse Large B-Cell Lymphoma Treated With First-Line Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone

2017 ◽  
Vol 35 (22) ◽  
pp. 2473-2481 ◽  
Author(s):  
Catherine Thieblemont ◽  
Hervé Tilly ◽  
Maria Gomes da Silva ◽  
Rene-Olivier Casasnovas ◽  
Christophe Fruchart ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Purpose The standard treatment of patients with diffuse large B-cell lymphoma (DLBCL) is rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Lenalidomide, an immunomodulatory agent, has shown activity in DLBCL. This randomized phase III trial compared lenalidomide as maintenance therapy with placebo in elderly patients with DLBCL who achieved a complete response (CR) or partial response (PR) to R-CHOP induction. Methods Patients with previously untreated DLBCL or other aggressive B-cell lymphoma were 60 to 80 years old, had CR or PR after six or eight cycles of R-CHOP, and were randomly assigned to lenalidomide maintenance 25 mg/d or placebo for 21 days of every 28-day cycle for 24 months. The primary end point was progression-free survival (PFS). Results A total of 650 patients were randomly assigned. At the time of the primary analysis (December 2015), with a median follow-up of 39 months from random assignment, median PFS was not reached for lenalidomide maintenance versus 58.9 months for placebo (hazard ratio, 0.708; 95% CI, 0.537 to 0.933; P = .01). The result was consistent among analyzed subgroups (eg, male v female, age-adjusted International Prognostic Index 0 or 1 v 2 or 3, age younger than 70 v ≥ 70 years), response (PR v CR) after R-CHOP, and positron emission tomography status at assignment (negative v positive). With longer median follow-up of 52 months (October 2016), overall survival was similar between arms (hazard ratio, 1.218; 95% CI, 0.861 to 1.721; P = .26). Most common grade 3 or 4 adverse events associated with lenalidomide versus placebo maintenance were neutropenia (56% v 22%) and cutaneous reactions (5% v 1%), respectively. Conclusion Lenalidomide maintenance for 24 months after obtaining a CR or PR to R-CHOP significantly prolonged PFS in elderly patients with DLBCL.

scholarly journals Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B)

2013 ◽  
Vol 24 (4) ◽  
pp. 1032-1037 ◽  
Author(s):  
N. Ketterer ◽  
B. Coiffier ◽  
C. Thieblemont ◽  
C. Fermé ◽  
J. Brière ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Low Risk ◽  
Phase Iii ◽  
Large B Cell Lymphoma ◽  
Phase Iii Study ◽  
Large B Cell

scholarly journals Addition of Lenalidomide to R-CHOP Improves Outcomes in Newly Diagnosed Diffuse Large B-Cell Lymphoma in a Randomized Phase II US Intergroup Study ECOG-ACRIN E1412

2021 ◽  
Vol 39 (12) ◽  
pp. 1329-1338 ◽  
Author(s):  
Grzegorz S. Nowakowski ◽  
Fangxin Hong ◽  
David W. Scott ◽  
William R. Macon ◽  
Rebecca L. King ◽  
...  
Keyword(s):  
B Cell ◽  
Phase Ii ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Newly Diagnosed ◽  
End Point ◽  
Large B Cell Lymphoma ◽  
Randomized Phase Ii ◽  
Large B Cell

PURPOSE Lenalidomide combined with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) (R2CHOP) in untreated diffuse large B-cell lymphoma (DLBCL) has shown promising activity, particularly in the activated B-cell–like (ABC) subtype. Eastern Cooperative Oncology Group (ECOG)-ACRIN trial E1412 was a randomized phase II study comparing R2CHOP versus R-CHOP in untreated DLBCL. PATIENTS AND METHODS Patients with newly diagnosed DLBCL, stage II bulky-IV disease, International Prognostic Index (IPI) ≥ 2, and ECOG performance status ≤ 2 were eligible and randomly assigned 1:1 to R2CHOP versus R-CHOP for six cycles. Tumors were analyzed using the NanoString Lymph2Cx for cell of origin. The primary end point was progression-free survival (PFS) in all patients with the co-primary end point of PFS in ABC-DLBCL. Secondary end points included overall response rate (ORR), complete response (CR) rate, and overall survival (OS). RESULTS Three hundred forty-nine patients were enrolled; 280 patients (145 R2CHOP and 135 R-CHOP) were evaluable: 94 were ABC-DLBCL, 122 germinal center B-cell–like-DLBCL, 18 unclassifiable, and 46 unknowns. Baseline characteristics were well-balanced between arms, and the median age was 66 (range, 24-92); 70% of patients had stage IV disease; 34%, 43%, and 24% had IPI 2, 3, and 4 or 5, respectively. Myelosuppression was more common in the R2CHOP arm. The ORR and CR rate were 92% and 68% in R-CHOP and 97% ( P = .06) and 73% ( P = .43) in the R2CHOP arm, respectively. The median follow-up was 3.0 years; R2CHOP was associated with a 34% reduction in risk of progression or death versus R-CHOP (hazard ratio [HR], 0.66 95% CI, 0.43 to 1.01) and 3-year PFS of 73% versus 61%, one-sided P = .03, and an improvement in OS (83% and 75% at 3 years; HR, 0.67; one-sided P = .05). The PFS HR for R2CHOP was 0.67 for ABC-DLBCL, one-sided P = .1. CONCLUSION In this signal-seeking study, the addition of lenalidomide to R-CHOP (R2CHOP) improved outcomes in newly diagnosed DLBCL including patients with ABC-DLBCL.

Young Patients With Non–Germinal Center B-Cell–Like Diffuse Large B-Cell Lymphoma Benefit From Intensified Chemotherapy With ACVBP Plus Rituximab Compared With CHOP Plus Rituximab: Analysis of Data From the Groupe d'Etudes des Lymphomes de l'Adulte/Lymphoma Study Association Phase III Trial LNH 03-2B

2014 ◽  
Vol 32 (35) ◽  
pp. 3996-4003 ◽  
Author(s):  
Thierry Jo Molina ◽  
Danielle Canioni ◽  
Christiane Copie-Bergman ◽  
Christian Recher ◽  
Josette Brière ◽  
...  
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Young Patients ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
Large B Cell Lymphoma ◽  
Germinal Center B Cell ◽  
Large B Cell

Purpose To determine whether any tumor biomarkers could account for the survival advantage observed in the LNH 03-2B trial among patients with diffuse large B-cell lymphoma (DLBCL) and low-intermediate risk according to the International Prognostic Index when treated with dose-intensive rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) compared with standard rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R-CHOP). Patients and Methods Using immunohistochemistry, expression of CD10, BCL6, MUM1, MYC, and BCL2 and coexpression of MYC/BCL2 were examined. The interaction effects between each biomarker and treatment arm on survival were studied in a restricted model and a full model incorporating clinical parameters. Results Among the 379 patients analyzed in the trial, 229 tumors were evaluable for germinal center B-cell–like (GCB)/non-GCB subclassification according to the Hans algorithm. Among all the biomarkers, only the interaction between the Hans algorithm and the treatment arm was significant for progression-free survival (PFS) and overall survival (OS) in univariable (PFS, P = .04; OS, P = .01) and multivariable (PFS, P = .03; OS, P = .01) analyses. Non-GCB tumors predicted worse PFS (hazard ratio [HR], 3.21; 95% CI, 1.29 to 8.00; P = .01) and OS (HR, 6.09; 95% CI, 1.37 to 27.03; P = .02) among patients treated with R-CHOP compared with patients who received R-ACVBP, whereas there were no significant survival differences between these regimens among patients with GCB tumors. Conclusion The survival benefit related to R-ACVBP over R-CHOP is at least partly linked to improved survival among patients with non-GCB DLBCL. Therefore, the Hans algorithm could be considered a theragnostic biomarker for selecting young patients with DLBCL who can benefit from an intensified R-ACVBP immunochemotherapy regimen.

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