Evaluation of the m7-FLIPI score in patients with follicular lymphoma revealed a promising predictive biomarker for determining suitable chemotherapy
The authors of a study presented at the December congress of the American Society of Hematology (ASH) in Orlando introduced a new prognostic tool, m7-FLIPI, for determining the risk level of patients with follicular lymphoma (FL). They tested its utility using samples from the GALLIUM clinical trial and, during the analysis, discovered a promising biomarker that could help in selecting the primary chemotherapy for FL patients.
m7-FLIPI Score
The clinical-genetic severity score for follicular lymphoma, m7-FLIPI, includes the mutational status of 7 genes (EZH2, ARID1A, MEF2B, EP300, FOXO1, CREBBP, and CARD11), the original FLIPI score (Follicular Lymphoma International Prognostic Index based on age, lactate dehydrogenase levels, hemoglobin, and extent of involvement), and the Eastern Cooperative Oncology Group performance status (ECOG PS).
The authors previously published findings that the integrated m7-FLIPI score improves risk stratification for patients with advanced-stage FL treated with immunochemotherapy. They tested it in groups of patients receiving rituximab in combination with chemotherapy. The aim of the current study was to verify the prognostic reliability of m7-FLIPI using samples and data from participants in the GALLIUM trial.
GALLIUM Trial
A total of 1202 patients with FL were enrolled in the clinical trial, randomized to receive rituximab or obinutuzumab in combination with chemotherapy (CHOP cohort: cyclophosphamide, vincristine, doxorubicin, prednisone; CVP cohort: cyclophosphamide, vincristine, prednisone; or bendamustine). The enrolled patients were previously untreated for FL, had advanced-stage disease, and an ECOG PS of 0–2.
In the study, targeted DNA sequencing was performed on FL tissue samples taken by biopsy for diagnosis. Genes frequently mutated (including those in the m7 group mentioned above) were selected. Data from 418 patients were used to evaluate m7-FLIPI. The median follow-up time for the analyzed cohort was 4.7 years; there were 283, 111, and 24 patients in the bendamustine, CHOP, and CVP cohorts, respectively.
Results of the m7-FLIPI Score Analysis
The m7-FLIPI score identified 104 patients as high-risk. Of the 194 patients initially classified as high-risk according to the FLIPI score, 90 were reclassified into the low-risk group by m7-FLIPI. High risk according to m7-FLIPI was associated with shorter progression-free survival (PFS) in the entire cohort (hazard ratio [HR] 1.52; p = 0.030).
The m7-FLIPI score had prognostic value in patients treated with rituximab-based therapy (HR 1.67; p = 0.037), but not in those treated with obinutuzumab-based therapy (HR 1.24; p = 0.49). Similarly, m7-FLIPI showed prognostic value for CHOP/CVP regimens (HR 2.05; p = 0.013) but not for bendamustine-based treatment (HR 1.23; p = 0.42). The m7-FLIPI score outperformed FLIPI (HR 1.34; p = 0.31) and had a significantly higher C-index (0.69 vs. 0.57; p = 0.021).
Mutational Status of the EZH2 Gene
The mutational status of the EZH2 gene had the greatest impact on the m7-FLIPI score. In the study, the EZH2 gene mutation was observed in 93 cases. It was associated with longer PFS (HR 0.25; p = 0.0036) in patients treated with CHOP/CVP but not in those treated with bendamustine (HR 1.11; p = 0.71). Interaction analysis indicated that patients with the EZH2 mutation benefit from CHOP/CVP regimens, while those without the mutation benefit more from bendamustine-based therapy, regardless of whether combined with rituximab or obinutuzumab.
Conclusion
The prognostic tool m7-FLIPI has been validated for patients treated with CHOP/CVP regimens. The mutational status of the EZH2 gene could become a new biomarker for determining suitable chemotherapy for FL patients. This gene encodes a methyltransferase that is involved in the suppression of the transcription of certain genes, particularly tumor suppressor genes.
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Source: Jurinovic V., Passerini V., Oestergaard M. Z. et al. Evaluation of the m7-FLIPI in patients with follicular lymphoma treated within the GALLIUM trial: EZH2 mutation status may be a predictive marker for differential efficacy of chemotherapy. 61st ASH annual meeting, Orlando, Florida, 2019 Dec 7.
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