MYC expression + BCL2 expression

Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy is the standard first-line treatment of DLBCL...Previous study has showed that ibrutinib combined with R-CHOP had improved event free survival (EFS) compared with placebo plus R-CHOP in non-GCB DLBCL patients with BCL2 and MYC co-expression (Johnson et al., Blood 2019)...Conclusions At the time of data cut-off 30 Jun 2023, 6 cycles of zanubrutinib combined with R-CHOP regimen was well tolerated and showed a promising response result in untreated non-GCB double-expression DLBCL patients. The study is ongoing and further results will be continuously released.

Unique patterns of oncogene co-expression at single-cell resolution affect clinical outcomes in DLBCL. Similar analyses evaluating oncogenic combinations at the cellular level may impact diagnostics and target discovery in other cancers.

We assessed whether high BCL2/MYC co-expression by RNA sequencing could identify a patient subset responsive to ibrutinib using baseline biopsies from the PHOENIX trial (NCT01855750), which evaluated the addition of ibrutinib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in untreated non-GCB DLBCL. Consequently, high BCL2/MYC co-expression identifies a subset of non-GCB DLBCL that may be preferentially responsive to ibrutinib and warrants further investigation. ClinicalTrials.gov NCT01855750.

Recently, Phoenix study demonstrate Ibrutinib plus R-CHOP improved EFS and OS (versus placebo plus R-CHOP) for DE-DLBCL younger patients. Despite of the small sample size and short follow-up time, ZRCHOP regimen achieved very high CR rate for DE DLBCL, and the toxicities were acceptable. Further study are required to prove the benefit of zanubrutinib when added to R-CHOP for newly-diagnosed DE-DLBCL. TP53 mutation , ATM mutation,P53 protein expression, and CD5 protein expression were probably the main reason for disease progression.