Clinicogenetic Risk Score May Identify High-Risk Follicular Lymphoma Patients

Prognostic score incorporating genetic and clinical information predicts first-line immunochemotherapy outcomes for advanced follicular lymphoma patients

medwireNews: Research suggests that a novel clinicogenetic risk score can significantly predict the likelihood of failure-free survival in patients with symptomatic, advanced stage or bulky Follicular lymphoma as they begin a first course of immunochemotherapy.

The model, m7-FLIPI, combines the mutational status of seven genes with the Follicular Lymphoma International Prognostic Index (FLIPI) and the Eastern Cooperative Oncology Group (ECOG) performance status, explain Oliver Weigert, from University Hospital of the Ludwig-Maximilians–University Munich in Germany, and team.

They suggest in The Lancet Oncology: “If validated in subsequent studies, the m7-FLIPI could be highly significant for the medical community, as high-risk patients are clearly underserved by current standard treatment and should be prioritised for innovative treatment options.”

The training cohort consisted of 151 phase III trial participants with previously untreated grade 1, 2 or 3A follicular lymphoma with B symptoms, bulky disease, impaired haemopoiesis or rapidly progressing disease who were unsuitable candidates for radiotherapy. All patients received first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone).

The 28% of patients with a high-risk m7-FLIPI score had a 5-year failure-free survival rate of 38.29% compared with a 5-year rate of 77.21% for the remaining patients with a low-risk score.

The clinicogenetic score outperformed prognostic models based only on the seven Gene Mutations or FLIPI-2 scores, the researchers note, giving a positive predictive value (PPV) and negative predictive value (NPV) of 64% and 78%, respectively.

m7-FLIPI was then tested in a validation cohort of 107 patients in a population-based registry with the same disease criteria who were treated with first-line R-CVP (rituximab, cyclophosphamide, vincristine and prednisone).

The 22% of patients with a high-risk m7-FLIPI score had a 5-year failure-free survival rate of 25.0% compared with 68.24% for the remaining patients with a low prognostic score. The PPV and NPV for 5-year failure-free survival were 72% and 68%, respectively, and the model outperformed FLIPI alone and combined with ECOG performance status.

The researchers say that their “stringent approach” to study design also led to the “unexpected finding” that the 66 patients in the training and validation cohorts who carried mutations in one of the seven genes examined, EZH2, all had low-risk m7-FLIPI scores, a “unique” transcriptional signature and favourable failure-free survival.

Indeed, Armando López-Guillermo, from Hospital Clínic in Barcelona, Spain, suggests in an accompanying comment that EZH2 “is a potential therapeutic target.”

He cautions that m7-FLIPI is only “marginally better” than FLIPI-2 at identifying high-risk patients, and that m7-FLIPI’s ability to predict treatment outcomes must be tested in prospective trials.

Nevertheless, the commentator concludes: “The clinicogenetic m7-FLIPI score represents the first step towards a bio-score in follicular lymphoma that is clinically relevant, reproducible, and feasible in clinical practice.”

References

Pastore A, Jurinovic V, Kridel R, et al. Integration of gene mutations in risk prognostication for patients receiving first-line immunotherapy for follicular lymphoma: a retrospective analysis of a prospective clinical trial and validation in a population-based registry. Lancet Oncol 2015; Advance online publication 6 August. DOI: http://dx.doi.org/10.1016/S1470-2045(15)00169-2

López-Guillermo A. A novel clinicogenetic prognostic score for follicular lymphoma. Lancet Oncol 2015; Advance online publication 6 August. DOI: http://dx.doi.org/10.1016/S1470-2045(15)00142-4

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