TY - JOUR
T1 - 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
AU - Nowakowski, Grzegorz S.
AU - Hong, Fangxin
AU - Scott, David W.
AU - Macon, William R.
AU - King, Rebecca L.
AU - Habermann, Thomas M.
AU - Wagner-Johnston, Nina
AU - Casulo, Carla
AU - Wade, James L.
AU - Nagargoje, Gauri G.
AU - Reynolds, C. M.
AU - Cohen, Jonathon B.
AU - Khan, Nadia
AU - Amengual, Jennifer E.
AU - Richards, Kristy L.
AU - Little, R. F.
AU - Leonard, John P.
AU - Friedberg, Jonathan W.
AU - Kostakoglu, Lale
AU - Kahl, Brad S.
AU - Witzig, Thomas E.
N1 - Publisher Copyright:
© 2021 by American Society of Clinical Oncology Creative Commons Attribution Non-Commercial No Derivatives 4.0 License
PY - 2021/4/20
Y1 - 2021/4/20
N2 - 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 5 .06) and 73% (P 5 .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 5 .03, and an improvement in OS (83% and 75% at 3 years; HR, 0.67; one-sided P 5 .05). The PFS HR for R2CHOP was 0.67 for ABC-DLBCL, one-sided P 5 .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.
AB - 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 5 .06) and 73% (P 5 .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 5 .03, and an improvement in OS (83% and 75% at 3 years; HR, 0.67; one-sided P 5 .05). The PFS HR for R2CHOP was 0.67 for ABC-DLBCL, one-sided P 5 .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.
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U2 - 10.1200/JCO.20.01375
DO - 10.1200/JCO.20.01375
M3 - Article
C2 - 33555941
AN - SCOPUS:85102964171
SN - 0732-183X
VL - 39
SP - 1329
EP - 1338
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 12
ER -