Adding Lenalidomide to R-CHOP Appears to Overcome Negative Prognostic Impact of the Non-Germinal Center B-Cell Phenotype in DLBCL


Key Points

  • The addition of lenalidomide to R-CHOP (R2CHOP) produced response in 98% of patients and complete response in 80% and was associated with 2-year event-free survival of 59% and overall survival of 78%.
  • There were no differences in 2-year progression-free survival or overall survival for patients with non–germinal center B-cell vs germinal center B-cell subtype receiving R2CHOP, whereas outcomes were significantly worse in historical controls with non–germinal center B-cell subtype receiving conventional R-CHOP.

A phase II study reported in the Journal of Clinical Oncology by Nowakowski et al indicates that the addition of lenalidomide (Revlimid) to R-CHOP (rituximab [Rituxan] plus cyclophosphamide, doxorubicin, vincristine, and prednisone)—a regimen known as R2CHOP—overcomes the negative prognostic effect of the non–germinal center B-cell phenotype in diffuse large B-cell lymphoma. The non–germinal center B-cell (or activated B-cell-like) subtype is associated with significantly worse outcomes with R-CHOP therapy compared with the germinal center B-cell subtype.

Study Details

In the study, adults with newly diagnosed untreated stage II to IV CD20-positive diffuse large B-cell lymphoma received oral lenalidomide at 25 mg/d on days 1 to 10 with standard-dose R-CHOP every 21 days for six cycles. All patients received pegfilgrastim (Neulasta) on day 2 of each cycle and aspirin prophylaxis throughout the study. Diffuse large B-cell lymphoma molecular subtype was determined by tumor immunohistochemistry and classified as germinal center B-cell vs non–germinal center B-cell in the R2CHOP patients and in 87 patients with diffuse large B-cell lymphoma in a historical control group from the Lymphoma Database who were treated with conventional R-CHOP.

Treatment Outcomes

Among 60 evaluable patients receiving R2CHOP, response was observed in 59 (98%), with complete response in 48 (80%). Two-year event-free survival was 59% (95% confidence interval [CI] = 48%–74%) and 2-year overall survival was 78% (95% CI = 68%–90%).

Non–Germinal B-Cell vs Germinal B-Cell Subtype

Analysis among 22 patients with the non–germinal center B-cell subtype and 33 with germinal center B-cell subtype who received R2CHOP showed no difference in 2-year progression-free survival (60% vs 59%, P = .83) or overall survival (83% vs 75%, P = .61). In contrast, among historical control group patients with non–germinal center B-cell subtype (n = 28) vs germinal center B-cell subtype (n = 59), 2-year progression-free survival (28% vs 64%, P < .001) and overall survival (46% vs 78%, P < .001) were significantly poorer in those with the non–germinal center B-cell subtype. 

Adverse Events

Nonhematologic adverse events of grade ≥ 3 occurred in 25% of R2CHOP patients (grade 4 in two patients); one patient had grade 5 sepsis. Hematologic adverse events of grade ≥ 3 occurred in 94%, with grade 4 events observed in 77%. Grade 3 and 4 neutropenia occurred in 13% and 77%, with grade 3 febrile neutropenia occurring in 9%, and grade 3 and 4 thrombocytopenia occurred in 27% and 17%.

The investigators concluded: “R2CHOP shows promising efficacy in [diffuse large B-cell lymphoma]. The addition of lenalidomide appears to mitigate a negative impact of [non–germinal center B-cell] phenotype on patient outcome.”

Grzegorz S. Nowakowski, MD, of Mayo Clinic, Rochester, Minnesota, is the corresponding author for the Journal of Clinical Oncology article. For full disclosures of the study authors, visit

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