TEST:

HTG EdgeSeq DLBCL Cell of Origin Assay

In preclinical studies, lenalidomide has been shown to induce cytotoxicity in ABC DLBCL cells by inhibiting NF-κB signaling and a synergistic effect is seen when B-cell receptor signaling is inhibited by the BTK inhibitor ibrutinib. The results of the BGB-3111-110 study demonstrated that the RP2D of zanubrutinib 160 mg twice daily plus lenalidomide 25 mg once daily had a manageable safety profile and promising efficacy in patients with R/R DLBCL. Similar efficacy was observed across DLBCL subtypes; ORR was numerically higher in the ABC subtype. Further molecular analysis is ongoing.

Our study demonstrated similar concordance with the HTG assay. As NGS platforms become more widely available in pathology, RNA expression-based assays are expected to become more significant in diagnostics and replace IHC-based methods of classification.

Patients with PD-L1 gene amplification, PD-L1+ tumor cells, and high mRNA levels of CD3D, HLA-DRA, and LAG3 in baseline tumor tissue may be more responsive to zanubrutinib and tislelizumab combination therapy. A high mRNA level of REL or mutations in TP53 may contribute to resistance of zanubrutinib and tislelizumab combination therapy. Due to the limited number of samples, results must be interpreted with caution.

Combined COO typing and whole transcriptome analysis from a single slide efficiently uses precious patient tissue. Longitudinal core needle sampling may yield insights into tumor evolution and therapeutic mechanisms of action across the DLBCL treatment landscape.