Value of MAP Signature and M7-FLIPI for Identifying Risk and Outcomes for Patients With Follicular Lymphoma

Identifying specific gene mutations at diagnosis through a mutations associated with progression (MAP) signature, and/or m7-Follicular Lymphoma International Prognostic Index (FLIPI) model may help identify prognostic factors for follicular lymphoma (FL), according to a clinicogenomic analysis published in Blood Advances. 

According to David A. Russler-Germain, MD, Washington University School of Medicine, St. Louis, Missouri, and coauthors, “Despite a growing understanding of FL pathogenesis, the translation of these insights into biology-informed clinical care has been slow. No predictive model exists to guide FL treatment [...]” The m7-FLIPI clinicogenomic risk model, which combines traditional FLIPI, patient performance status, and mutation statuses of 7 genes, is a potential strategy for predicting follicular lymphoma outcomes. 

In this analysis, the study authors aimed to assess the ability and success of this model, and MAP signature, in particular, in the prognosis of follicular lymphoma. Genomic profiling was performed on a total of 370 patients with FL or FL with aggressive histological transformation (t-FL). Grade, stage, watch-and-wait, and progression of follicular lymphoma within 24 months (POD24) did not differ by mutation burden. Conversely, mutation burden was significantly higher among patients with relapsed/refractory (R/R) FL and t-FL compared to newly diagnosed (dx) FL. There was no association between mutation burden and frontline progression-free survival among patients with dx-FL. 

Mutations in 20 genes, including 6 significantly mutated genes (SMGs), were more commonly observed in R/R FL and t-FL than in dx-FL. The 6 SMGs consisted of STAT6, TP53, IGLL5, B2M, SOCS1, and MYD88. The study authors noted that a MAP signature is defined as ≥2 mutations in the 6 SMGs, plus the CREBBP gene, or 7 genes total. Notably, patients with dx-FL who had a MAP signature had shorter frontline progression-free survival. This indicates that the 7-gene set may factor into FL progression risk and be potentially more generalizable than the m7-FLIPI, which had “modest” prognostic value among these patients. 

In conclusion, in this study specific gene mutations helped identify high-risk patients with follicular lymphoma. Additionally, the m7-FLIPI model predicted prolonged remissions among patients with FL undergoing standard treatment, or rituximab plus chemotherapy. 

Dr Russler-Germain, et al, noted, “Future studies are warranted to validate the poor prognosis associated with a MAP signature in dx FL, potentially facilitating novel trials specifically in this high-risk subset of patients.”

Source: 

Russler-Germain DA, Krysiak K, Ramirez C, et al. Mutations associated with progression in follicular lymphoma predict inferior outcomes at diagnosis: Alliance A151303. Blood Adv. Published online: September 15, 2023. doi: 10.1182/bloodadvances.2023010779