The combination of lenalidomide plus rituximab appeared highly active in patients with treatment-naive indolent non-Hodgkin’s lymphoma, according to results of an open-label phase 2 trial.
The trial included 110 patients with stage III or stage IV follicular lymphoma (n=50), marginal zone lymphoma (n=30) or small lymphocytic lymphoma (n=30) treated at The University of Texas MD Anderson Cancer Center.
Patients with follicular lymphoma and marginal zone lymphoma received 20 mg daily lenalidomide (Revlimid, Celgene) on days 1 to 21 of each 28-day cycle. Patients with small lymphocytic lymphoma started with doses of 10 mg daily to prevent tumor flare, and daily dosing increased by 5 mg each month until it reached 20 mg daily. Patients received a 375 mg/m2 IV infusion of rituximab (Rituxan; Genentech, Biogen Idec) on day 1 of each cycle.
Patients who demonstrated response after six cycles had the option to continue treatment for a total of 12 cycles.
Overall response, defined as the combination of complete and partial responses, served as the primary endpoint.
The final analysis included 103 evaluable patients, including 46 with follicular lymphoma, 27 with marginal zone lymphoma and 30 with small lymphocytic lymphoma.
Overall, researchers observed complete responses in 65 (63%; 95% CI, 53-72) patients and partial responses in 28 (27%; 95% CI, 19-37).
Researchers reported an 87% complete response rate and 11% partial response rate among patients with follicular lymphoma; a 67% complete response rate and 22% partial response rate among patients with marginal zone lymphoma; and a 23% complete response rate and 57% partial response rate among patients with small lymphocytic lymphoma.
The most common grade 3 or grade 4 adverse events were neutropenia (35%); muscle pain (9%); rash (7%); cough, dyspnea or other pulmonary symptoms (5%); fatigue (5%), thrombosis (5%) and thrombocytopenia (5%).
“Lenalidomide plus rituximab is well tolerated and highly active as initial treatment for indolent non-Hodgkin’s lymphoma,” the researchers concluded. “The encouraging results of this trial have laid the foundation for an international phase 3 registration study to investigate this promising non-chemotherapy approach in patients with untreated follicular lymphoma.”
The findings need to be validated in large randomized studies, but the international, randomized RELEVANCE trial — which will compare lenalidomide and rituximab vs. rituximab plus chemotherapy — “is an important step in this respect,” Christian Buske, MD, of the Comprehensive Cancer Center Ulm at the Institute of Experimental Cancer Researcher University Hospital Ulm in Germany, wrote in an accompanying editorial.
“If this trial’s results are positive for rituximab plus lenalidomide, it will have the potential to challenge our current treatment strategy in advanced stage follicular lymphoma and will bring the chemotherapy-free approach to the front of our therapeutic arsenal,” Buske wrote. “Ongoing large randomized trials will ultimately enable us to decide whether our hope for chemotherapy-free management of advanced stage indolent lymphoma was justified, but we should be optimistic.”
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Disclosure: The study was funded by Celgene. The researchers report research funding and honoraria from, grant support from, advisory roles with and data monitoring committee roles with Celgene, Gilead and Roche. Buske reports consultant roles with Celgene, Janssen, Pharmacyclics, Pfizer and Roche, as well as research funding from Janssen and Roche.