Journal Article

Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma: an open-label, phase 2 trial

Shah, Jatin, Neelapu, Sattva S, Kwak, Larry W, Oki, Yasuhiro, Baladandayuthapani, Veerabhadran, Fanale, Michelle A, Westin, Jason R, Orlowski, Robert Z, Fowler, Nathan H, Nastoupil, Loretta, Rawal, Seema, Hagemeister, Fredrick B, Samaniego, Felipe, Romaguera, Jorge E, Wang, Michael, Muzzafar, Tariq, Fayad, Luis E, McLaughlin, Peter, Tsai, Kenneth Y, Claret, Linda C, Turturro, Francesco, Davis, R Eric, Feng, Lei

2014

Overview

Standard treatments for indolent non-Hodgkin lymphomas are often toxic, and most patients ultimately relapse. Lenalidomide, an immunomodulatory agent, is effective as monotherapy for relapsed indolent non-Hodgkin lymphoma. We assessed the efficacy and safety of lenalidomide plus rituximab in patients with untreated, advanced stage indolent non-Hodgkin lymphoma. In this phase 2 trial, undertaken at one instution, patients with follicular lymphoma and marginal zone lymphoma were given lenalidomide, orally, at 20 mg/day on days 1–21 of each 28-day cycle. For patients with small lymphocytic lymphoma, dosing began at 10 mg/day to avoid tumour flare, with an escalation of 5 mg/month to 20 mg/day. Rituximab was given at 375 mg/m2 as an intravenous infusion on day 1 of each cycle. Patients responding after six cycles could continue therapy for up to 12 cycles. The primary endpoint was overall response, defined as the proportion of patients who achieved a partial or complete response; patients were assessed for response if they had any post-baseline tumour assessment. This trial is registered with ClinicalTrials.gov, number NCT00695786. 110 patients with follicular lymphoma (n=50), marginal zone lymphoma (n=30), and small lymphocytic lymphoma (n=30) were enrolled from June 30, 2008, until Aug 12, 2011. 93 of 103 evaluable patients had an overall response (90%, 95% CI 83–95). Complete responses occurred in 65 (63%, 95% CI 53–72) and partial responses in 28 patients (27%, 19–37). Of 46 evaluable patients with follicular lymphoma, 40 (87%) patients had a complete response and five (11%) had a partial response. Of 27 evaluable patients with marginal zone lymphoma, 18 (67%) had a complete response and six (22%) had a partial response. Of 30 evaluable patients with small lymphocytic lymphoma, seven (23%) had a complete response and 17 (57%) had a partial response. The most common grade 3 or 4 adverse events were neutropenia (38 [35%] of 110 patients), muscle pain (ten [9%]), rash (eight [7%]), cough, dyspnoea, or other pulmonary symptoms (five [5%]), fatigue (five [5%]), thrombosis (five [5%]), and thrombocytopenia (four [4%]). Lenalidomide plus rituximab is well tolerated and highly active as initial treatment for indolent non-Hodgkin lymphoma. An international phase 3 study (NCT01476787) to compare this regimen with chemotherapy in patients with untreated follicular lymphoma is in progress. Celgene Corporation and Richard Spencer Lewis Memorial Foundation and Cancer Center Support Grant.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adult / Aged / Aged, 80 and over / Antibodies, Monoclonal, Murine-Derived - administration & dosage / Antibodies, Monoclonal, Murine-Derived - adverse effects / Antineoplastic Combined Chemotherapy Protocols / Biopsy / Bone marrow / Cancer / Cancer therapies / Chemotherapy / Cytotoxicity / Disease-Free Survival / Drug Administration Schedule / Female / Hematology / Hematology, Oncology and Palliative Medicine / Humans / Infections / Lymphoma / Lymphoma, Follicular - drug therapy / Lymphoma, Follicular - pathology / Lymphoma, Non-Hodgkin - drug therapy / Lymphoma, Non-Hodgkin - pathology / Male / Medical imaging / Middle Aged / Neoplasm Recurrence, Local - drug therapy / Neoplasm Recurrence, Local - pathology / Neoplasm Staging / Nuclear medicine / Rituximab / Thalidomide - administration & dosage / Thalidomide - adverse effects / Thalidomide - analogs & derivatives / Treatment Outcome