FDA Clears Diagnostic Assay for B-Cell Lymphoma

The FDA has granted 510(k) clearance for the Ventana Kappa and Lambda Dual ISH mRNA Probe Cocktail, a highly sensitive in-situ hybridization (ISH) assay designed to assist pathologists in diagnosing B-cell lymphoma by differentiating a B-cell malignancy from a normal, reactive response to an infection, allowing for faster access to treatment.1

This novel test is the first clinically approved ISH assay capable of evaluating the full spectrum of B-cell lymphoma subtypes of over 65 biomarkers, including plasma cell neoplasms, on a single tissue slide. The assay previously received marketing authorization in Europe in June 2024.

“Accurately differentiating lymphoma from an infection is critical in ensuring accurate and timely diagnosis, especially as the symptoms can appear similar,” Jill German, head of the Pathology Lab at Roche Diagnostics, stated in a news release. “With this new test, clinicians can have confidence in their diagnosis, while the test reduces the need for multiple samples and time-consuming follow-up tests, giving patients certainty sooner, and enabling faster access to the right treatment.”

The assay’s accuracy was validated in a study comparing its performance with flow cytometry and immunohistochemistry (IHC), which are considered the current standards of practice for the diagnosis of B-cell lymphoma.2 Investigators used samples from 79 cases of B-cell lymphoma across various subtypes, including follicular lymphoma (n = 36), mantle cell lymphoma (n = 6), marginal zone lymphoma (n = 12), lymphoplasmacytic lymphoma (n = 6), small lymphocytic lymphoma (n = 4), and diffuse large B-cell lymphoma (n = 15), which were previously confirmed using formalin-fixed paraffin-embedded biopsies.

At data cutoff, 49.4% (n = 39/79) of cases were classified as kappa light chain restricted, and 36.7% (n = 29/79) were defined as lambda light chain restricted; 11.3% (n = 9/79) were classified as indeterminate. Among the 70 cases with kappa or lambda light chain restricted classification by chromogenic in situ hybridization (CISH), 98.6% were concordant with the reference methods of flow cytometry or IHC, and the discordance rate was 1.4%.

Based on these findings, study authors concluded that the optimized CISH method detected lower levels of mRNA vs current slide-based methods, highlighting the ability to conduct clonality assessments via FFPE biopsies in mature B cell neoplasms. CISH was highly accurate compared with flow cytometry or IHC.

The mRNA Probe Cocktail enables the detection of kappa and lambda immunoglobulin light chain expression, providing pathologists with the ability to assess both markers on the same slide. This feature aids in differentiating between reactive processes and B-cell malignancies, including mature B-cell lymphomas and plasma cell neoplasms. By integrating the assessment of both markers, the assay delivers diagnostic certainty, particularly when traditional biopsy results are inconclusive.

This test is not intended as a standalone diagnostic tool and must be interpreted by a qualified pathologist in the context of the patient’s clinical history and other diagnostic tests.1 It is indicated for use when a biopsy of lymph node or bone marrow indicates inconclusive results in order to differentiate between a reactive process or B-cell lymphoma and plasma cell neoplasms.

References

1. Roche receives FDA clearance for new, highly sensitive test to aid clinicians in diagnosing B-cell lymphoma. News release. Roche. January 13, 2025. Accessed January 16, 2025. https://diagnostics.roche.com/us/en/news-listing/2025/roche-receives-fda-clearance-for-new-highly-sensitive-test-to-aid-clinicians-in-diagnosing-b-cell-lymphoma.html
2. Rimsza LM, Day WA, McGinn S, et al. Kappa and lambda light chain mRNA in situ hybridization compared to flow cytometry and immunohistochemistry in B cell lymphomas. Diagn Pathol. 2014;9:144. Published online July 21, 2014. doi:10.1186/1746-1596-9-144