Combination Targeted Therapy in Relapsed Diffuse Large B-Cell Lymphoma

作者：Christopher Melani, Rahul Lakhotia, Stefania Pittaluga, James D. Phelan, Da Wei Huang, George W. Wright, Jillian Simard, Jagan Muppidi, Craig J. Thomas, Michele Ceribelli, Frances A. Tosto, Yandan Yang, Weihong Xu, Theresa Davies‐Hill, Svetlana Pack, Cody J. Peer, Oluwatobi Arisa, Esther Mena, Liza Lindenberg, Ethan Bergvall, Craig A. Portell, Rafic Farah, Seung‐Tae Lee, Amynah Pradhan, Candis Morrison, Atekelt Tadese, Anna Marie Juanitez, Crystal Lu, Allison P. Jacob, Heidi Simmons, William D. Figg, Seth M. Steinberg, Elaine S. Jaffe, Mark Roschewski, Louis M. Staudt, Wyndham H. Wilson · 发表于：New England Journal of Medicine · 年份：2024 · DOI：10.1056/nejmoa2401532 · 被引用次数：71 · 研究领域：Lymphoma Diagnosis and Treatment、CAR-T cell therapy research、Protein Degradation and Inhibitors

Background The identification of oncogenic mutations in diffuse large B-cell lymphoma (DLBCL) has led to the development of drugs that target essential survival pathways, but whether targeting multiple survival pathways may be curative in DLBCL is unknown. Methods We performed a single-center, phase 1b–2 study of a regimen of venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide (ViPOR) in relapsed or refractory DLBCL. In phase 1b, which included patients with DLBCL and indolent lymphomas, four dose levels of venetoclax were evaluated to identify the recommended phase 2 dose, with fixed doses of the other four drugs. A phase 2 expansion in patients with germinal-center B-cell (GCB) and non-GCB DLBCL was performed. ViPOR was administered every 21 days for six cycles. Results In phase 1b of the study, involving 20 patients (10 with DLBCL), a single dose-limiting toxic effect of grade 3 intracranial hemorrhage occurred, a result that established venetoclax at a dose of 800 mg as the recommended phase 2 dose. Phase 2 included 40 patients with DLBCL. Toxic effects that were observed among all the patients included grade 3 or 4 neutropenia (in 24% of the cycles), thrombocytopenia (in 23%), anemia (in 7%), and febrile neutropenia (in 1%). Objective responses occurred in 54% of 48 evaluable patients with DLBCL, and complete responses occurred in 38%; complete responses were exclusively in patients with non-GCB DLBCL and high-grade B-cell lymphoma with rearrangements of MY...