Dr Cortese on the Benefits of a Multiomic Evaluation of Immunologic Changes in CLL After Venetoclax

“[If there are] methyl groups added onto the DNA that can block transcription, [it can] further affirm that [we’re] seeing a true biological signature. It’s going through a multiomic sandwich, and it self-validates without many patient samples needed, which I think is really cool.”

Matthew Cortese, MD, MPH, an assistant professor in the Department of Medicine–Lymphoma and Department of Cancer Genetics and Genomics at Roswell Park Comprehensive Cancer Center, discusses the benefits of a multiomic evaluation of immunologic changes in a smaller patient population of patients with chronic lymphocytic leukemia (CLL) following treatment with venetoclax (Venclexta).

Preliminary findings from an analysis presented at the 2024 ASH Annual Meeting demonstrated that treatment with venetoclax was associated with immune synapse repair with complex mechanisms beyond clearance of malignant CLL cells. The bioinformatic process of multiomics integrates data from several biological layers into a comprehensive model. Specifically, after covariate adjustment for treatment responses at 30 days, T cells, natural killer cells, and macrophages were repaired after treatment with venetoclax at 400 mg daily in patients with CLL (n = 13).

Although the analysis only included 13 patients with CLL, the process of multiomics self-validates itself without the need for a larger patient population, Cortese begins. A benefit of multiomics includes layering several data streams simultaneously, he explains. For example, when signals of 1 BCL2 gene emerge from the data streams, it can be found in the transcriptomic profile, which shows where BCL2 is located in the pathway map, he says. When these are linked to metabolites that offshoot from the respective pathway, all changes within the data streams are shown, he adds.

Furthermore, these streams allow for the evaluation of methylation, groups of which can be added to the DNA and block transcription, according to Cortese. The entire process further affirms a true biological signature and helps establish all of the layered data streams, he concludes.