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.

Abstract

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.

• Authors: Grzegorz S Nowakowski, Fangxin Hong, David W Scott, William R Macon, Rebecca L King, Thomas M Habermann, Nina Wagner-Johnston, Carla Casulo, James L Wade, Gauri G Nagargoje, C M Reynolds, Jonathon B Cohen, Nadia Khan, Jennifer E Amengual, Kristy L Richards, R F Little, John P Leonard, Jonathan W Friedberg, Lale Kostakoglu, Brad S Kahl, Thomas E Witzig
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 39 Issue 12 Pg. 1329-1338 (04 20 2021) ISSN: 1527-7755 [Electronic] United States
• PMID: 33555941 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• R-CHOP protocol
• Rituximab
• Vincristine
• Doxorubicin
• Cyclophosphamide
• Lenalidomide
• Prednisone

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Cyclophosphamide (administration & dosage, adverse effects)
• Doxorubicin (administration & dosage, adverse effects)
• Female
• Humans
• Lenalidomide (administration & dosage, adverse effects)
• Lymphoma, Large B-Cell, Diffuse (drug therapy, mortality)
• Male
• Middle Aged
• Prednisone (administration & dosage, adverse effects)
• Rituximab (administration & dosage, adverse effects)
• Vincristine (administration & dosage, adverse effects)
• Young Adult