The prognostic value of the M7-follicular lymphoma (FL) international prognostic index (FLIPI) may be dependent on treatment regimen, according to results from a study published in the British Journal of Haematology.
FL is a highly heterogeneous disease with a variable clinical course. The M7-FLIPI incorporates the FLIPI score, mutational status from 7 genes (EZH2, ARID1A, MEF2B, EP300, FOXO1, CREBBP and CARD11), and performance status to stratify patients into low- and high-risk categories according to 5-year failure-free survival after frontline chemoimmunotherapy. This stratification, however, may not properly place patients who receive a chemotherapy-free immunotherapy regimen.
In this study, researchers assessed the predictive value of M7-FLIPI in 95 patients with FL from 2 randomized clinical trials on indolent lymphoma from the Nordic Lymphoma Group. These patients received either rituximab monotherapy or rituximab with interferon alfa-2a.
A targeted panel of the 7 genes included in the M7-FLIPI was used to calculate the score; 81% (77/95) of patients were categorized as low-risk, 18% (17/95) were categorized as high-risk, and risk status was not known in 1 patient.
At median follow-up of 10.6 years, 76% of patients were alive. Time to treatment failure (TTF) was defined as the time between the initiation of trial therapy and the start of new therapy or death. Results indicated no difference in TTF between the M7-FLIPI low- and high-risk groups (log-rank P =.94).
Similarly, no difference in OS between the M7-FLIPI low- and high-risk groups occurred (log-rank P =.99).
Mutational status was found to be associated with TTF for 2 different genes. Mutated EZH2 was associated with longer TTF (median, 7.8 vs 2.7 years; hazard ratio (HR), 0.55; 95% CI, 0.30-0.99; P =.05). Mutated EP300 was associated with shorter TTF (median, 1.1 vs 4.1 years; HR, 2.2; 95% CI, 1.17-4.13; P =.01).
“We conclude from our study of a FL cohort with more than 10 years of median follow-up that prognostic factors may have different significance when applied in a context of first-line treatment with immunotherapy instead of immunochemotherapy,” wrote the authors. “Whether similar conclusions can be drawn in the context of novel drugs, such as immunomodulators and checkpoint inhibitors, remains to be shown.”
1. Lockmer S, Ren W, Brodtkorb M, et al. M7-FLIPI is not prognostic in follicular lymphoma patients with first-line rituximab chemo-free therapy [published online August 18, 2019]. Br J Haematol. doi:10.1111/bjh.16159