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The Clinical Utility of Updated Immunophenotyping Guidelines in Follicular Lymphoma
Current NCCN Guidelines recommend molecular testing for patients with follicular lymphoma, which has improved diagnostic accuracy and can assist in selecting the appropriate treatment in certain cases.
Updates in immunophenotyping guidelines and the incorporation of advanced molecular testing, specifically next generation sequencing (NGS), have refined the diagnostic approach for follicular lymphoma. These changes in the NCCN Guidelines intend to bolster diagnostic quality rather than overhaul current treatment protocols, though a few key exceptions exist that influence therapeutic decisions.
A significant shift in the guidelines involves the meticulous evaluation of follicular lymphoma variants, notably those that do not present the common t(14;18) chromosomal translocation. When morphological assessment points to follicular lymphoma but standard FISH testing for the translocation is negative, NGS can be a highly valuable diagnostic tool. The crucial role of NGS in these t(14;18)-negative cases is to search for specific genetic signatures. For instance, the identification of a STAT6 mutation confirms a variant form of follicular lymphoma. Recognizing this variant is essential, as it is associated with a unique clinical course and dictates the need for specialized treatment. Furthermore, other markers on the NGS panel, including CREBBP and MAP kinase, serve to reinforce confidence in the overall follicular lymphoma diagnosis.
Beyond enhancing diagnostic clarity, NGS carries direct clinical utility. The most immediate therapeutic implication comes from detecting EZH2 mutations. This mutation is relevant because tazemetostat is designed to target EZH2. While the medication shows efficacy in both patients with and without the mutation, the clinical response is demonstrably enhanced in those carrying the EZH2 mutation. Therefore, the adoption of NGS and updated immunophenotyping provides a dual benefit: ensuring accurate classification, especially for the challenging t(14;18)-negative variant, and identifying patients who are most likely to benefit from EZH2-directed treatment.
