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Integration of Mutation Status to FLIPI Improves Risk Stratification for Patients Receiving First-Line Immunochemotherapy for Follicular Lymphoma

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Key Points

  • A clinicogenetic risk model was developed consisting of mutation status of seven genes (EZH2, ARID1A, MEF2B, EP300, FOXO1, CREBBP, and CARD11), FLIPI score, and ECOG performance status.
  • The m7-FLIPI model outperformed FLIPI in distinguishing high vs low risk for failure-free survival in patients receiving first-line immunotherapy for follicular lymphoma.

In a study reported in The Lancet Oncology, Pastore et al found that the addition of mutation status of seven genes to the Follicular Lymphoma International Prognostic Index (FLIPI) and Eastern Cooperative Oncology Group (ECOG) performance status produced a clinicogenetic model (m7-FLIPI) with high prognostic ability in patients receiving first-line immunotherapy for follicular lymphoma.

Study Details

In the study, DNA deep sequencing was performed to retrospectively analyze mutation status of 74 genes in biopsy specimens from 151 patients (training cohort) obtained within 1 year before beginning immunochemotherapy with rituximab (Rituxan), cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in a phase III trial. A clinicogenetic risk model (m7-FLIPI) including mutation status of 7 selected genes (EZH2, ARID1A, MEF2B, EP300, FOXO1, CREBBP, and CARD11), FLIPI score, and ECOG performance status, was assessed in the training cohort (median follow-up of 7.7 years) and in a population-based validation cohort of 107 patients using specimens obtained within 1 year before beginning first-line immunochemotherapy with rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP; median follow-up of 6.7 years).

Failure-Free Survival

In the training cohort, m7-FLIPI identified a high-risk group (28% of patients) with 5-year failure-free survival of 38.29% vs 77.21% for the low-risk group (hazard ratio [HR] = 4.14, P < .0001), outperforming a model using only gene mutations (HR = 3.76, P < .0001). The model had positive and negative predictive values of 64% and 78% and a C-index of 0.80.

In the validation cohort, m7-FLIPI defined a high-risk group (22% of patients) with 5-year failure-free survival of 25.00% vs 68.24% for the low-risk group (HR = 3.58, P < .0001), outperforming FLIPI alone (HR = 2.18, 95% confidence interval [CI] = 1.21–3.92) and FLIPI combined with ECOG performance status (HR = 2.03, 95% CI = 1.12–3.67). The model had positive and negative predictive values of 72% and 68% and a C-index of 0.79.

Overall Survival

High-risk m7-FLIPI was associated with significantly poorer 5-year overall survival in the training cohort (65.25% vs 89.98%, P = .00031) and in the validation cohort (41.67% vs 84.01%, P < .0001) and outperformed FLIPI alone in both cohorts.

The investigators concluded: “Integration of the mutational status of seven genes with clinical risk factors improves prognostication for patients with follicular lymphoma receiving first-line immunochemotherapy and is a promising approach to identify the subset at highest risk of treatment failure.”

Oliver Weigert, MD, of University Hospital of the Ludwig-Maximilians-University, is the corresponding author of The Lancet Oncology article.

The study was funded by Deutsche Krebshilfe and Terry Fox Research Institute. For full disclosures of the study authors, visit www.thelancet.com/journals/lanonc.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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