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Lymphoma

Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trial

Abstract

Lenalidomide–rituximab therapy is effective in grade 1–2 follicular and mantle cell lymphoma, but its efficacy in diffuse large B-cell lymphoma (DLBCL), transformed large cell lymphoma (TL) and grade 3 follicular lymphoma (FLG3) is unknown. In this phase II trial, 45 patients with relapsed or refractory DLBCL (n=32), TL (n=9) or FLG3 (n=4) who had received 1–4 prior lines of treatment were given 20 mg oral lenalidomide on days 1–21 of each 28-day cycle, and intravenous rituximab (375 mg/m2) weekly during cycle 1. Grade 3/4 hematological toxicities included neutropenia (53%), lymphopenia (40%), thrombocytopenia (33%), leukopenia (27%) and anemia (18%), with a median follow-up time of 29.1 months (range 14.7–52.0 months). Overall response (OR) rate was 33%; median response duration was 10.2 months. Median progression-free survival (PFS) and overall survival (OS) were 3.7 and 10.7 months, respectively. Nine of the 15 responding patients (three partial response (PR), six complete response (CR)) proceeded with stem cell transplantation (SCT) and were censored at the time of transplantation. When data were analyzed without censoring, median PFS remained 3.7 months and response duration increased to 30.9 months. Rituximab plus oral lenalidomide is well tolerated and effective for patients with relapsed/refractory DLBCL and TL. SCT after lenalidomide–rituximab is associated with prolonged response duration.

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Correspondence to M Wang or N Fowler.

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Competing interests

Michael Wang, Sattva Neelapu, Larry Kwak and Nathan Fowler have received research support from Celgene Corporation in conducting the preclinical and clinical trials. Michael Wang has received honoraria for speaking on Celgene Corporation products. Nathan Fowler and Sattva Neelapu have consultant or advisory relationships with the Celgene Corporation.

Author Contributions

Michael Wang, Liang Zhang and Jorge Romaguera designed the study. Michael Wang, Nicolaus Wagner-Bartak, Fredrick Hagemeister, Sattva Neelapu, Peter McLaughlin, Anas Younes, Maria Badillo, Maria Bejarano and Yiming Chen collected and assembled the data. Michael Wang, Luis Fayad, Nicolaus Wagner-Bartak, Fredrick Hagemeister, Anas Younes, Jorge Romaguera, Larry Kwak, Richard Champlin, Ken H Young, Lei Feng, Luis Fayad, Michele Fanale, Nathan Fowler and Saatva Neelapu analyzed and interpreted the data. Michael Wang, Luis Fayad, Nicolaus Wagner-Bartak, Liang Zhang, Kate Newberry, Madhav Desai, Fredrick Hagemeister, Sattva Neelapu, Peter McLaughlin, Michelle Fanale, Anas Younes, Nathan Fowler, Ken H Young, Richard Champlin, Larry Kwak, Lei Feng, Maria Badillo, Maria Bejarano, Yiming Chen and Jorge Romaguera wrote the manuscript. Nathan Fowler, Jorge Romageura, Sattva Neelapu, Richard Champlin, Michelle Fanale, Yasuhiro Oki, Barbara Pro, Alma Rodriguez, Jatin Shah, Sheeba Thomas, Anas Younes and Fredrick Hagemeister provided study materials or patients. All authors approved the final manuscript.

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Wang, M., Fowler, N., Wagner-Bartak, N. et al. Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trial. Leukemia 27, 1902–1909 (2013). https://doi.org/10.1038/leu.2013.95

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