Predicting early relapse in follicular lymphoma: have we turned a corner?

Background Patients with follicular lymphoma (FL) have heterogeneous outcomes. Predictor models able to distinguish, at diagnosis, patients at high versus low risk of progression are still needed. Methods The primary objective of this study was to use gene-expression profiling data to build a signature predictive of outcome in patients treated in the rituximab era. In a retrospectively assembled training cohort of 134 pretreatment FL patients from the prospective randomized PRIMA trial, we developed an expression-based predictor of progression-free survival (PFS) that was further evaluated in FFPE samples obtained from three independent international cohorts, using NanoString technology. The validation cohorts comprised a distinct set of patients from the PRIMA trial (n=178), a cohort from the University of Iowa/Mayo Clinic Lymphoma SPORE (n=201) and the Hospital Clinic University of Barcelona (n=109). All tissue samples consisted of pretreatment diagnostic biopsies and were confirmed as FL grade 1-3a. The patients were all treated with regimens containing rituximab and chemotherapy, possibly followed by either rituximab maintenance or ibritumomab-tiuxetan consolidation. Findings The expression levels of 395 genes were associated with a risk of progression. Twenty-three genes reflecting both B-cell biology and tumor microenvironment were retained to build a predictive model, which identified a population at an increased risk of progression (p