Effect of ibrutinib with R-CHOP chemotherapy in genetic subtypes of DLBCL
Wyndham H Wilson, George W Wright, Da Wei Huang, Brendan Hodkinson, Sriram Balasubramanian, Yue Fan, Jessica Vermeulen, Martin Shreeve, Louis M Staudt, Wyndham H Wilson, George W Wright, Da Wei Huang, Brendan Hodkinson, Sriram Balasubramanian, Yue Fan, Jessica Vermeulen, Martin Shreeve, Louis M Staudt
Abstract
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.
Keywords: ABC DLBCL; BTK inhibitor; CD79B; MYD88; NOTCH1; cancer genomics; memory B cell; precision medicine.
Conflict of interest statement
Declaration of interests L.M.S., G.W., and D.W.H. are inventors on an NIH patent application covering the LymphGen algorithm. L.M.S., G.W., D.W.H., W.H.W., S.B., and B.H. are inventors on an NIH patent application covering the use of BTK inhibitors in genetic subtypes of DLBCL. B.H., S.B., Y.F., J.V., and M.S. are employees of Johnson & Johnson.
Published by Elsevier Inc.
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Source: PubMed