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Effect of ibrutinib with R-CHOP chemotherapy in genetic subtypes of DLBCL
Cancer Cell  (IF31.743),  Pub Date : 2021-11-04, DOI: 10.1016/j.ccell.2021.10.006
Wyndham H. Wilson, George W. Wright, Da Wei Huang, Brendan Hodkinson, Sriram Balasubramanian, Yue Fan, Jessica Vermeulen, Martin Shreeve, Louis M. Staudt

In diffuse large B cell lymphoma (DLBCL), tumors belonging to the ABC but not GCB gene expression subgroup rely upon chronic active B cell receptor signaling for viability, a dependency that is targetable by ibrutinib. A phase III trial (“Phoenix;” ClinicalTrials.gov: NCT01855750) showed a survival benefit of ibrutinib addition to R-CHOP chemotherapy in younger patients with non-GCB DLBCL, but the molecular basis for this benefit was unclear. Analysis of biopsies from Phoenix trial patients revealed three previously characterized genetic subtypes of DLBCL: MCD, BN2, and N1. The 3-year event-free survival of younger patients (age ≤60 years) treated with ibrutinib plus R-CHOP was 100% in the MCD and N1 subtypes while the survival of patients with these subtypes treated with R-CHOP alone was significantly inferior (42.9% and 50%, respectively). This work provides a mechanistic understanding of the benefit of ibrutinib addition to chemotherapy, supporting its use in younger patients with non-GCB DLBCL.