Combination Targeted Therapy in Relapsed Diffuse Large B-Cell Lymphoma
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
Abstract
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: (or both). Circulating tumor DNA was undetectable in 33% of the patients at the end of ViPOR therapy. With a median follow-up of 40 months, 2-year progression-free survival and overall survival were 34% (95% confidence interval [CI], 21 to 47) and 36% (95% CI, 23 to 49), respectively. CONCLUSIONS: Treatment with ViPOR was associated with durable remissions in patients with specific molecular DLBCL subtypes and was associated with mainly reversible adverse events. (Funded by the Intramural Research Program of the National Cancer Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health and others; ClinicalTrials.gov number, NCT03223610.).