CD79A mutation

P3, N=302, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2024 --> May 2025 | Trial primary completion date: May 2024 --> May 2025

We have reviewed the complex role of CD79a/CD79b in multiple aspects of normal B cell biology and how is the normal BCR signaling affected by lymphoid neoplasms associated CD79A/CD79B mutations. We have also summarized important unresolved questions and highlighted issues that remain to be explored for better understanding of CD79a/CD79b-mediated signal transduction and the eventual identification of additional therapeutically targetable BCR signaling vulnerabilities.

PVRL, as well as secondary vitreoretinal lymphomas after PCNSL or extracerebral DLBCL, have high mutation frequencies in characteristically mutated genes in PCNSL or MCD/cluster 5 type DLBCL. Supporting diagnostics, mutation detection can also be performed on cell-free DNA from the vitreous supernatant.

We retrospectively reviewed R/R DLBCL patients who were administered with Zanubrutinib 160mg*bid plus BR (Bendamustine 90mg/㎡*d1-2+Rituximab 375mg/㎡*d0)or R2 (Lenalidomide 25mg* d1-21 +Rituximab 375mg/㎡*d0)in our center between January, 2019 and July, 2023. Zanubrutinib combined with BR or R2 showed promising efficacy and acceptable safety in R/R DLBCL patients, which may be a potential treatment option for autologous stem cell transplantation-ineligible R/R DLBCL patients.

Although preliminary, the responders to the OR induction therapy may attain a synergistic antitumor effect and thus achieve a high CRR when receiving subsequent O+R-CHOP. The safety was favorable. More updated data will be presented from this ongoing study.

This is the first reporting molecular classification and their clinical significance in PCNS-DLBCL of Asian population. MCD subtype was prevalent but has no prognostic power in PCNS-DLBCL. Further larger study is needed.

Rescue experiments with CD79B wild-type restored surface expression of CD79A and IgM with mature glycosylation, whereas a naturally occurring CD79B G137S mutant disrupting CD79A/CD79B heterodimerization did not. Our study highlights that CD79A and CD79B are required for surface IgM expression in human B cells and illuminates the importance of the IgM expression level for signaling and fitness.

Rescue experiments with CD79B wild-type restored surface expression of CD79A and IgM with mature glycosylation, whereas a naturally occurring CD79B G137S mutant disrupting CD79A/CD79B heterodimerization did not. Our study highlights that CD79A and CD79B are required for surface IgM expression in human B cells and illuminates the importance of the IgM expression level for signaling and fitness.

Zanubrutinib (160 mg po bid) plus R-CHOP (ZR-CHOP) was administered in TN cohort, and Zanubrutinib (160 mg po bid) combined with investigator-determined conventional salvage chemotherapy (CSC, including ICE, DHAP, GDP, or GemOx, +/- rituximab) was administered in R/R cohort. CD79A/CD79B mutation was frequent in DLBCL patients, especially in R/R cases. Zanubrutinib combined with immunochemotherapy showed encouraging activity and acceptable tolerance in pts with CD79A/CD79B-mutant DLBCL. TP53 mutation seemed to be a detrimental factor.

Zanubrutinib (160 mg po bid) plus R-CHOP (ZR-CHOP) was administered in TN cohort, and Zanubrutinib (160 mg po bid) combined with investigator-determined conventional salvage chemotherapy (CSC, including ICE, DHAP, GDP, or GemOx, +/- rituximab) was administered in R/R cohort. TP53 mutation seems to be a detrimental factor. The study is still ongoing and it is worth looking forward to updating the long-term survival data.