Arima Genomics, Inc., a cancer diagnostics company bringing DNA sequence and structure together to advance cancer diagnosis and therapy selection, today announced results from a study conducted with Duke University and recently published in Blood Advances. The study demonstrated the value of broad structural rearrangement profiling in diffuse large B-cell lymphoma (DLBCL), with Arima Hi-C technology identifying clinically important rearrangements missed or not evaluated by routine fluorescence in situ hybridization (FISH) and providing fusion-partner and structural information inaccessible to current FISH testing.

The study evaluated the same proprietary Hi-C sequencing approach used in Aventa™ Lymphoma, Arima’s clinical test for fusion and rearrangement detection in B- and T-cell lymphomas from routine FFPE tumor tissue. Aventa Lymphoma adds a broader structural view when targeted testing leaves important diagnostic or molecular questions unresolved.

“FISH remains one of the cornerstone tools in lymphoma diagnostics, but targeted testing begins with a predefined question,” said Ken H. Young, MD, PhD, Professor, Vice Chair and Director of the Hematopathology Division at Duke University School of Medicine. “By identifying rearrangements without requiring every target or fusion partner to be anticipated, this approach can provide important additional information when a case is complex or existing findings are insufficient to support a definitive diagnosis or accurate classification.”

Researchers analyzed archival FFPE specimens from 159 patients drawn from a consecutive case series of de novo DLBCL assembled by the International DLBCL Rituximab-CHOP Consortium Program. All patients were treated with R-CHOP and had previously undergone FISH testing for MYC, BCL2 and BCL6 rearrangements as part of their diagnostic workup.

After review of discordant results and available orthogonal validation, Arima Hi-C detected 102 of 106 (96%) adjudicated MYC, BCL2 and BCL6 rearrangements, compared with 81 of 106 (76%) detected by FISH. Of the 106 rearrangements, 25 were detected by Arima Hi-C but not by FISH; four were detected by FISH but not by Hi-C.

These rearrangements can have important implications for lymphoma classification and clinical management. Concurrent MYC and BCL2 rearrangements, for example, define a distinct high-grade B-cell lymphoma entity, and inform classification, risk assessment and treatment planning.

The study also demonstrated the value of looking beyond the genes routinely evaluated by FISH. Arima Hi-C identified 45 additional clinically relevant rearrangements or fusions in 42 patients, representing 26% of the cohort. These involved CCND1, CCND3, IRF4, PD-L1, ALK, MALT1 and ATM.

Of these, 22 rearrangements in 20 patients were characteristic of other lymphoma types. Findings involving CCND1 raised differential diagnostic questions involving mantle cell lymphoma and DLBCL, while rearrangements involving IRF4, ALK and MALT1 provided additional diagnostic context. PD-L1 rearrangements may have implications for treatment or clinical trial eligibility.

The additional findings reflect how the technologies interrogate structural variation differently. FISH evaluates predefined genomic targets using specific probe locations. Arima Hi-C detects rearrangements through structural relationships across the genome, without requiring the breakpoint or fusion partner to be anticipated. It can also reveal fusion partners and broader structural context that break-apart FISH generally does not provide.

Many MYC rearrangements detected by Arima Hi-C but not by FISH involved non-immunoglobulin partners. The reasons why FISH did not definitively identify rearrangements detected by Arima Hi-C included cryptic breakpoints, faint or complex FISH signals, results below established FISH positivity thresholds, unbalanced rearrangements indeterminate by FISH, or tissue-related technical issues.

Additional findings were also associated with clinically relevant disease features. Excluding additional BCL6 findings, patients with rearrangements detected by Hi-C but missed or not evaluated by FISH had significantly poorer progression-free survival. In germinal center B-cell-like DLBCL, nearly all cases with additional MYC or BCL2 rearrangements detected by Hi-C also showed gene-expression patterns associated with high-grade lymphoma biology.

“The value of Arima Hi-C isn’t simply that it can identify additional rearrangements,” said Anthony Schmitt, PhD, Senior Vice President, Science, at Arima Genomics. “While it provides a broader structural view without requiring every target or fusion partner to be anticipated, the key value of Aventa Lymphoma is that it enables comprehensive genomic analysis from a single tissue sample, and we are developing analysis methods that reveal other genomic variants such as copy number variants and small variants in future products to enable truly comprehensive genomic profiling of tumors.”

About Aventa Lymphoma

Aventa Lymphoma is a whole-genome, NGS-based clinical test for fusion and rearrangement detection in B- and T-cell lymphomas. Leveraging Arima’s proprietary Hi-C sequencing technology and reporting on 417 genes, the test is designed to identify clinically relevant rearrangements without requiring predefined breakpoint locations or fusion partners. Aventa Lymphoma provides structural genomic information that can aid diagnosis, classification, prognosis and therapy selection, including in cases where targeted testing is inconclusive or does not fully explain the clinical and pathologic findings.

Learn more at www.aventatest.com/aventalymphoma.

About Arima Genomics

Arima Genomics is a cancer diagnostics company redefining cancer testing by bringing DNA sequence and structure together. Built on leadership in 3D genome science and proprietary Hi-C sequencing technology, Arima develops clinical tests that reveal cancer-driving alterations conventional approaches can miss or incompletely characterize. Through its Aventa clinical testing brand, Arima offers testing for solid tumors and lymphoma from its CLIA-certified laboratory in Orlando, Florida.

Learn more at www.arimagenomics.com and www.aventatest.com, and follow Arima Genomics on LinkedIn.

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