Effect of ibrutinib with R-CHOP chemotherapy in genetic subtypes of DLBCL
| Autor: | Brendan Hodkinson, Louis M. Staudt, George E. Wright, Martin Shreeve, Sriram Balasubramanian, Yue Fan, Wyndham H. Wilson, Da-Wei Huang, Jessica Vermeulen |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
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 |
| Zdroj: | Cancer cell. 39(12) |
| ISSN: | 1878-3686 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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