As reported in the Journal of Clinical Oncology, Maurer et al have developed FLIPI24, a modern prognostic model for newly diagnosed follicular lymphoma.
As stated by the investigators, “Although most patients with … [follicular lymphoma] can expect an indolent course, progressive lymphoma remains the primary cause of death during the first decade after diagnosis. Progression of disease within 24 months … of starting first-line … immunochemotherapy defines a high-risk population with poor survival, but better risk stratification at diagnosis is needed.”
Study Details
The FLIPI24 model was developed and internally validated to predict 24-month event rates using individual data from 4,485 patients treated with first-line immunochemotherapy in 10 observational follicular lymphoma cohorts. The final model consisted of age and the blood-based variables of hemoglobin, lactate dehydrogenase, beta-2 microglobulin, and white blood cell count, with scoring used to distinguish high-, intermediate-, and low-risk groups. External validation was performed using the prospective observational Lymphoma Epidemiology of Outcomes (LEO) cohort (n = 565) and three randomized phase III trial cohorts (PRIMA, RELEVANCE, and GALLIUM; n = 3,192).
Key Findings
In the four external first-line immunochemotherapy validation cohorts, patients with high-risk FLIPI24 (23%–32% of patients) had significantly higher 24-month event rates (22%–35%) and poorer 5-year overall survival (77%–83%) vs patients with low-risk FLIPI24 (29%–31% of patients), who had 24-month event rates of 10% to 12% and 5-year overall survival of 96% to 97%. Patients with intermediate-risk FLIPI24 (40%–43% of patients) had 24-month event rates of 12% to 19% and 5-year overall survival of 91% to 92%.
For the FLIPI24 low-, intermediate-, and high-risk categories, lymphoma-related mortality was 3.9%, 5.5%, and 15.6% at 5 years in the LEO cohort; 1.8%, 3.5%, and 9.3% at 5 years in the GALLIUM cohort; 0.7%, 4.3%, and 9.5% at 5 years in the RELEVANCE cohort; and 1.8%, 4.6%, and 11.1% at 5 years and 3.8%, 7.0%, and 16% at 10 years in the PRIMA cohort.
The c-statistic scores for overall survival in the LEO, PRIMA, RELEVANCE, and GALLIUM cohorts were, respectively, 0.708, 0.679, 0.705, and 0.695 using the FLIPI24 model; these scores were superior to the scores of 0.627, 0.659, 0.661, and 0.626 achieved with the FLIPI risk model, and 0.638, 0.594, 0.588, and 0.628 achieved with the PRIMA risk model.
The investigators concluded: “… FLIPI24 provides improved risk stratification over existing clinical models in newly diagnosed [follicular lymphoma]…. FLIPI24 can be used to enrich future clinical trial designs in newly diagnosed [follicular lymphoma].”
Matthew J. Maurer, ScD, of Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute, Lymphoma Research Foundation, and others. For full disclosures of all study authors, visit ascopubs.org.
