Integrated multiomic molecular analyses reveal key gene expression patterns and tumor evolution dynamics, predicting improved outcomes and reduced toxicity from combination therapy in patients with relapsed/refractory T-cell lymphomas

BostonGene, a leading provider of AI-based molecular and immune profiling solutions, and researchers from multiple cancer centers including, Memorial Sloan Kettering Cancer Center, Dana-Farber Cancer Institute, Weill Cornell Medicine and Washington University School of Medicine in St. Louis and others, today announced the online publication of the manuscript “Deep Clinical Responses and Limited Inflammatory Toxicity in Patients with Relapsed/Refractory T-cell Lymphomas Receiving Duvelisib and Romidepsin”* in Nature Medicine. The study highlights significant clinical responses and reduced inflammatory toxicity in patients with relapsed and refractory T-cell lymphomas treated with a combination of duvelisib and romidepsin.

Historically, PI3K inhibitors have been associated with autoimmune and infectious toxicities, often leading to market withdrawals. Researchers from multiple leading cancer centers had previously demonstrated single-agent activity of the PI3K-γδ inhibitor duvelisib in T-cell lymphomas, although inflammatory adverse events were noted. Based on this preliminary work, a new phase 1b/2a clinical trial was launched to investigate the safety and efficacy of duvelisib in combination with either romidepsin or bortezomib in patients with relapsed/refractory T-cell lymphomas. Combining duvelisib and romidepsin significantly improved treatment outcomes in patients with peripheral T-cell lymphomas (PTCL).

To explore tumor molecular features that may be linked to therapeutic response to this novel therapeutic combination, BostonGene performed DNA whole exome (WES) and RNA transcriptome (RNAseq) sequencing on both pre-treatment and on-treatment biopsies. BostonGene then performed integrated multi-omic molecular analyses, including cellular deconvolution, mutational landscape analyses, longitudinal genetic reconstruction to study tumor evolution, and deciphering immune microenvironment dynamic changes. BostonGene uncovered that PTCL patients with a follicular helper T-cell subtype showed increased response rates to the combination and identified gene expression patterns potentially linked to therapeutic resistance.

“Our findings offer a promising new approach for treating patients with relapsed and refractory T-cell lymphomas, specifically those with the follicular helper T-cell subtype. We are excited about the potential of this combination therapy to improve patient outcomes and expand treatment options in this challenging disease,” said Nathan Fowler, MD, Chief Medical Officer at BostonGene.

*Research conducted in collaboration with Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, Dana-Farber Cancer Institute, Washington University School of Medicine in St. Louis, Stanford University, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center Collaborative Innovation Center for Cancer Medicine, Merck and Co.

About BostonGene Corporation

BostonGene is a software-driven biotechnology company at the intersection of technology and biology, dedicated to advancing and personalizing cancer medicine. Founded in 2015, BostonGene has continuously pushed the boundaries of innovation to improve patient care and accelerate drug development. Our AI-powered multiomics platform decodes cancer patients' molecular profiles, including their immune system and tumor microenvironment, to uncover key disease drivers, identify novel drug targets and recommend the most effective treatments. With advanced bioanalytics, an indication-specific cancer library and a next-generation CLIA-certified, CAP-accredited high-complexity laboratory, we deliver precise, clinically validated insights that propel precision medicine and advance oncology research. For more information, visit www.BostonGene.com.

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