Gene-Expression Profiling Score for Predicting High- vs Low-Risk of Follicular Lymphoma Progression
As reported in The Lancet Oncology, Huet et al have developed a 23-gene expression profile that predicts risk of follicular lymphoma progression.
Study Details
In a training cohort consisting of a subgroup of patients from the PRIMA trial (in which rituximab [Rituxan] maintenance was evaluated after rituximab plus chemotherapy induction), 23 genes (of 395 candidates) reflecting B-cell biology and tumor microenvironment with correlation coefficients greater than 0.75 between two technologies used for gene expression profiling (Affymetrix U133 Plus 2.0 microarrays and NanoString technology) were retained in a model that identified a subgroup of patients at increased risk of progression.
In a multivariate Cox model for progression-free survival adjusted for rituximab maintenance treatment and Follicular Lymphoma International Prognostic Index (FLIPI) 1 score, the model independently predicted progression (adjusted hazard ratio [aHR] for high-risk group vs low-risk group = 3.68, P < .0001). Five-year progression-free survival was 26% in the high-risk group vs 73% in the low-risk group.
Validation Cohorts
The model was examined using NanoString technology to digitally quantify gene expression in 488 formalin-fixed, paraffin-embedded samples from a distinct PRIMA trial cohort (cohort 1, n = 178), University of Iowa/Mayo Clinic Lymphoma SPORE project cohort (cohort 2, n = 201), and Barcelona Hospital Clinic cohort (cohort 3, n = 109). All patients were treated with regimens containing rituximab and chemotherapy, followed in some cases by either rituximab maintenance or ibritumomab-tiuxetan (Zevalin) consolidation.
The performance of the model was confirmed in each of the validation cohorts, with aHRs for progression-free survival for high-risk vs low-risk groups of 2.57 (95% confidence interval [CI] = 1.65–4.01] in cohort 1, 2.12 (95% CI = 1.32–3.39) in cohort 2, and 2.11 (95% CI = 1.01–4.41) in cohort 3. For the pooled validation cohorts, median progression-free survival was 3.1 years in the high-risk group and 10.8 years in the low-risk group (P < .0001). The risk of progression at 2 years was 38% vs 19%. In multivariate analysis, the model predicted progression-free survival independently of anti–CD20 maintenance treatment and of FLIPI score (aHR for the pooled cohort = 2.30, 95% CI = 1.72–3.07).
The investigators concluded, “We developed and validated a robust 23-gene expression-based predictor of progression-free survival that is applicable to routinely available formalin-fixed, paraffin-embedded tumour biopsies from patients with follicular lymphoma at time of diagnosis. Applying this score could allow individualised therapy for patients according to their risk category.”
The study was funded by Roche, SIRIC Lyric, LYSARC, National Institutes of Health, Henry J. Predolin Foundation, and Spanish Plan Nacional de Investigacion.
Gilles Salles, MD, of the Service d’Hematologie Clinique, Centre Hospitalier Lyon Sud, is the corresponding author for The Lancet Oncology article.
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