1. Effect of ibrutinib with R-CHOP chemotherapy in genetic subtypes of DLBCL
- Author
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Brendan Hodkinson, Louis M. Staudt, George E. Wright, Martin Shreeve, Sriram Balasubramanian, Yue Fan, Wyndham H. Wilson, Da-Wei Huang, and Jessica Vermeulen
- Subjects
Oncology ,Male ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,R-CHOP chemotherapy ,chemistry.chemical_compound ,Piperidines ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Bruton's tyrosine kinase ,Humans ,Memory B cell ,Cyclophosphamide ,Aged ,Chemotherapy ,biology ,business.industry ,Adenine ,CD79B ,Middle Aged ,medicine.disease ,Survival benefit ,chemistry ,Doxorubicin ,Vincristine ,Ibrutinib ,biology.protein ,Prednisone ,Female ,Lymphoma, Large B-Cell, Diffuse ,business ,Rituximab ,Diffuse large B-cell lymphoma - Abstract
Summary 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.
- Published
- 2021