TY - JOUR
T1 - Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma
T2 - An open-label, phase 2 trial
AU - Fowler, Nathan H.
AU - Davis, R. Eric
AU - Rawal, Seema
AU - Nastoupil, Loretta
AU - Hagemeister, Fredrick B.
AU - McLaughlin, Peter
AU - Kwak, Larry W.
AU - Romaguera, Jorge E.
AU - Fanale, Michelle A.
AU - Fayad, Luis E.
AU - Westin, Jason R.
AU - Shah, Jatin
AU - Orlowski, Robert Z.
AU - Wang, Michael
AU - Turturro, Francesco
AU - Oki, Yasuhiro
AU - Claret, Linda C.
AU - Feng, Lei
AU - Baladandayuthapani, Veerabhadran
AU - Muzzafar, Tariq
AU - Tsai, Kenneth Y.
AU - Samaniego, Felipe
AU - Neelapu, Sattva S.
N1 - Publisher Copyright:
© 2014 Elsevier Ltd.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - Background: 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. Methods: 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. Findings: 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%]). Interpretation: 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. Funding: Celgene Corporation and Richard Spencer Lewis Memorial Foundation and Cancer Center Support Grant.
AB - Background: 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. Methods: 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. Findings: 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%]). Interpretation: 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. Funding: Celgene Corporation and Richard Spencer Lewis Memorial Foundation and Cancer Center Support Grant.
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U2 - 10.1016/S1470-2045(14)70455-3
DO - 10.1016/S1470-2045(14)70455-3
M3 - Article
C2 - 25439689
AN - SCOPUS:84908574357
SN - 1470-2045
VL - 15
SP - 1311
EP - 1318
JO - The lancet oncology
JF - The lancet oncology
IS - 12
ER -