The addition of lenalidomide may ameliorate the negative effect of [non–germinal center B-cell] phenotype on outcome.
—Grzegorz S. Nowakowski, MD
The combination of lenalidomide (Revlimid) and rituximab (Rituximab), dubbed the “R-squared” regimen, has gained attention lately, and ongoing trials are evaluating whether chemotherapy with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone) can be improved by adding a nonchemotherapeutic agent like lenalidomide. At the 2014 ASCO Annual Meeting, researchers reported encouraging results of this approach in diffuse large B-cell lymphoma, especially with the non–germinal center B-cell (non-GCB) phenotype.1
Phase II Study
In a phase II study of 64 patients with newly diagnosed diffuse large B-cell lymphoma, the addition of lenalidomide to R-CHOP (R2-CHOP), appeared to reduce the negative prognostic significance of the non–germinal center B-cell phenotype, producing progression-free and overall survival rates similar to those observed in the germinal center B-cell subtype, reported Grzegorz S. Nowakowski, MD, Assistant Professor of Medicine at the Mayo Clinic, Rochester, Minnesota.
“The addition of lenalidomide may ameliorate the negative effect of [non–germinal center B-cell] phenotype on outcome,” Dr. Nowakowski said.
The R2-CHOP treatment consisted of 25 mg lenalidomide daily on days 1 to 10 of a 21-day cycle in addition to standard R-CHOP given every three cycles. The population had a median age of 65, with 20% older than 70 years. Sixty percent had stage IV disease, and about half the patients were considered high-risk.
Among 55 evaluable patients, 33 were of the germinal center B-cell phenotype and 22 were non–germinal center B-cell patients. The R2-CHOP regimen was associated with similar outcomes in both subtypes, with 2-year progression-free survival of 60% and 50%, respectively, and 2-year survival rates of 83% and 75%, Dr. Nowakowski said.
The response rate was 98%, and 80% of patients had complete responses.
The R2-CHOP regimen was well tolerated, even in the older patients, he said. The most frequent grade 3/4 toxicity was neutropenia (87%), but febrile neutropenia was rare. Grade 3/4 thrombocytopenia (44%) and anemia (15%) were observed in some patients.
A case-matched historical analysis showed that outcomes with R-CHOP were substantially worse among patients with non–germinal center B-cell phenotype than for those with germinal center B-cell diffuse large B-cell lymphoma. At 2 years, 64% of germinal center B-cell patients were progression-free, compared to only 28% of the non–germinal center B-cell population treated with R-CHOP (P = .00029). However, in the R2-CHOP treatment arms, these rates were 59% and 60%, respectively (P = .83).
Similarly, 2-year overall survival was 74% and 46%, respectively, in the R-CHOP treatment arms (P = .000036), but were comparable in the R2-CHOP arms—75% and 83%, respectively
(P = .61).
These findings suggest that the addition of lenalidomide to R-CHOP may overcome the negative prognostic impact associated with the non–germinal center B-cell phenotype, he suggested.
A randomized trial, Eastern Cooperative Oncology Group (ECOG) 1412, is currently comparing R2-CHOP vs R-CHOP for the initial treatment of diffuse large B-cell lymphoma. The study is also enrolling patients through the Alliance and SWOG. ■
Disclosure: Dr. Nowakowski and his coauthors reported no potential conflicts of interest.
1. Nowakowski GS, LaPlant B, Macon WR, et al: Effect of lenalidomide combined with R-CHOP (R2CHOP) on negative prognostic impact of nongerminal center phenotype in newly diagnosed diffuse large B-cell lymphoma: A phase 2 study. ASCO Annual Meeting. Abstract 8520. Presented June 1, 2014.
The ASCO Post asked for comment about the presentation by Nowakowski et al from Nathan Fowler, MD, who developed and led many of the early studies of R-Squared (lenalidomide [Revlimid], rituximab [Rituxan]), in lymphoma as well. Dr. Fowler is Associate Professor in the Department of...