A study presented at the European Hematology Association (EHA) Virtual Meeting (June 11-21, 2020) sought to identify biomarkers in patients with relapsed or refractory non-germinal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL) treated with zanubrutinib.
The non-GCB subtype of DLBCL is associated with poor clinical outcomes. While Bruton’s tyrosine kinase (BTK) inhibitors have demonstrated activity in mantle cell lymphoma, chronic lymphocytic leukemia, and Waldenström macroglobulinemia, only modest activity has been shown in DLBCL.
A group of Chinese researchers designed a study to evaluate potential biomarkers that can predict response to zanubrutinib—a highly selective covalent BTK inhibitor—in relapsed or refractory non-GCB DLBCL. A total of 121 patients were sampled from four zanubrutinib clinical studies that were conducted at a similar time period. Of the studies, two involved zanubrutinib monotherapy (n = 79) and the remaining two involved zanubrutinib combined with an anti-CD20 antibody therapy (n = 42).
Researchers also performed a subgroup analysis of 56 patients who were subtyped by gene expression profiling using the HTG EdgeSeq DLBCL Cell of Origin Assay.
Results of the analysis showed that the unadjusted objective response rate (ORR) was between 23% and 35% across all four studies. Forty-nine patients had gene expression profiling-confirmed activated B-cell DLBCL classification. Among these patients, the ORR was between 36% and 54% and comparable for zanubrutinib monotherapy (42.1%) and combination therapy (45.5%).
Researchers also found that among the 56 patients with HTG gene expression profiles, PAX5 expression was significantly higher in responders to zanubrutinib monotherapy, and PIM1, BCL2, and FOXP1 expression were substantially higher in responders to combination therapy.
Additionally, they found that patients with MYC and BCL2 double expressor DLBCL had higher ORRs, longer progression-free survival, and longer overall survival. Among 77 patients who were tested by next-generation sequencing, mutations in B-cell receptor pathway or NOTCH1 pathway genes correlated with better response to therapy.
Furthermore, researchers noted that patients with CD79B mutations (n = 25) had significantly higher ORR than those without CD79B mutations (n = 52).
“Zanubrutinib alone or in combination with an anti-CD20 antibody showed activity in the overall non-GCB DLBCL population,” authors of the study concluded. “The retrospective biomarker analysis identified subsets of patients (such as PAX5-high or with CD79B mutations) with higher response rates to zanubrutinib treatment.”—Zachary Bessette
