TEST:

Oncomine™ BCR IGH-LR Assay

Multi-isotype clonal lineages are automatically reported by the software and provide a means to directly monitor isotype switching events in the context of antigen challenge or immunomodulation. Taken together, we anticipate this assay to be a useful tool for biomarker analysis of adenosine pathway inhibition immunotherapy.

We successfully validated and adopted an NGS-based assay to evaluate IGVH SHM status in patients with CLL. Our clinical laboratory experience performing this assay has demonstrated superior performance by the NGS method in terms of ease of use, assay robustness, reliability, and clinical usefulness.

Concordant results were shown between FR1 and Leader-targeting primers using DNA input showing the utility in both priming locations. Orthogonal testing of the Leader-J assay showed excellent concordance for mutation rate, SHM status, and stereotypy.

"These results support highly multiplexed long-read next-generation sequencing (NGS) assays to quantify SHM in either DNA or RNA samples. Concordant results were shown between FR1 and Leader-targeting primers using DNA input showing the utility in both priming locations. RNA-based NGS methods benefit from lower sample requirements as well as the addition of isotype identification, opening new research areas for study of the B-cell immune repertoire."

"Here, we performed TCR sequencing in patients from the phase 2 trial SAKK 16/14 undergoing neoadjuvant chemotherapy with three cycles of cisplatin/docetaxel followed by treatment with the PD-L1 antibody durvalumab. In contrast, TMB was not associated with EFS, MPR or nodal clearance (p=0.91, p=0.47, p=0.52). Conclusion Our results show that TCR repertoire measured in peripheral blood samples and tumor tissue may provide a useful tool for predicting risk of recurrence after neoadjuvant sequential chemo-immunotherapy with durvalumab in patients with resectable stage IIIA(N2) NSCLC."

IGHV gene mutational status has continued to be one of the most robust prognostic markers in CLL; furthermore, it has a strong predictive value for response to treatment with U‐CLL displaying shorter progression‐free survival after chemo‐immunotherapy with the fludarabine, cyclophosphamide and rituximab (FCR) regimen compared to M‐CLL. The assay will also enable the detection of a clone at very low frequency e.g. following treatment or at clonal evolution. In addition, isotype identification may be of interest in translational research and potentially provide information about the dynamics of the clone.