Patients with certain subtypes of diffuse large B-cell lymphoma (DLBCL) have better survival with ibrutinib plus R-CHOP vs R-CHOP alone, according to research published in Cancer Cell.

Genetic subtypes of DLBCL lead to differences in treatment responses, and at least 7 genetic subtypes are recognized. The phase 3 PHOENIX trial ( Identifier: NCT01855750) showed a survival benefit of ibrutinib for patients with DLBCL who have an ABC gene expression subtype. The current research analyzed biopsies from the Phoenix trial to determine whether patients with certain genetic subtypes received a significant survival advantage with ibrutinib.

The analysis included DLBCL tumors from 773 of the 838 patients in the PHOENIX trial. 340 patients (44%) were aged 60 or younger.

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Non-GCB DLBCL has 4 genetic subtypes: MCD, BN2, N1 and A53. Patients with the MCD subtype were primarily ABC DLBCL, and patients with the BN2 and N1 subtype were more often GCB and unclassified. The authors were not able to identify patients with A53 subtype with the available data.

Patients older than 60 have an increased toxicity with ibrutinib, and do not benefit from the treatment regardless of genetic subtype. The authors analyzed event-free survival (EFS) and overall survival (OS) for younger patients.

Patients younger than 60 years with an MCD (n=31) subtype had 100% 3-year EFS and OS with ibrutinib plus rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP) compared to an EFS of 48% and OS of 69.9% when treated with R-CHOP alone. Patients with N1 DLBCL (n=13) had a 3-year EFS and OS of 100%, compared to an EFS and OS of 50% with R-CHOP alone.

Patients with BN2 DLBCL did not benefit from ibrutinib. The authors also extended the LymphGen subtype classification to include probable cases. A survival benefit with ibrutinib was still seen for patients with MCD and N1 DLBCL.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Wilson WH, Wright GW, Huang DW, et al. Effect of ibrutinib with R-CHOP chemotherapy in genetic subtypes of DLBCL. Published online November 3, 2021. Cancer Cell. doi:10.1016/j.ccell.2021.10.006