Neither the FLIPI Nor the FLIPI2 Accurately Segregates Low- Risk From Intermediate- Risk Follicular Lymphoma Patients in Terms of Progression-Free Survival

Follicular Lymphoma International Prognostic Index (FLIPI) is the most frequently used prognostic index for risk stratification in follicular lymphoma (FL) patients. The FLIPI was designed retrospectively in the pre-rituximab era, with overall survival (OS) as the end-point. Follicular Lymphoma International Prognostic Index 2 (FLIPI2) is a more recent index designed prospectively in the rituximab era to overcome these drawbacks.

To compare the efficacy of the FLIPI and FLIPI2 prognostic indexes in discriminating patients with FL with a distinct outcome in terms of OS and progression-free survival (PFS).

From 1985 to 2007, 302 patients were newly diagnosed with grade 1–3a FL in our institution. The FLIPI could be retrospectively assigned in 220 patients and the FLIPI2 in 149 patients. The 122 patients (47 male/75 female; median age: 56 years –range: 25–87) in whom both the FLIPI and FLIPI2 indexes were assessable constitute the study population. Seventy-five patients (61%) received treatment immediately after diagnosis (of which, 25 patients received rituximab containing regimens), whereas the remainder were managed expectantly. Main characteristics at diagnosis are as follows: age>60 years, 41%; stage III-IV, 70%; Hb<12 g/L, 17%; bone marrow involvement, 45%; largest lymph node diameter>6cm, 26%; B2M>ULN, 20% and LDH>ULN, 17%. The median follow-up for alive patients was 86 months (range: 12– 270).

Five-year OS and PFS were 74% (95%CI: 69–79) and 38% (95%CI: 32–44), respectively, for the 302 patients. There were no significant differences in the outcome of these patients in comparison with the 122 patients comprising the study population. The distribution of the 122 patients according to the FLIPI and FLIPI2 as well as the 5-year OS and 5-year PFS are shown in the table. The FLIPI and the FLIPI2 indexes predicted OS (p<0.0001 both for the FLIPI and the FLIPI2), but the FLIPI2 did not accurately separate patients with low-risk from those with intermediate risk in terms of OS (p=0.3). The FLIPI score predicted PFS (p=0.001) but was not able to discriminate patients with low-risk from those with intermediate-risk (p=0.6). There was a trend for the FLIPI2 to predict PFS (p=0.06) but it did not segregate the low-risk group from the intermediate-risk group (p=0.3)

The FLIPI separates patients into 3 risk groups, well-balanced in terms of the proportion of patients in each group with a distinct OS. In contrast the, majority of the patients fall into the intermediate risk group according to the FLIPI2, and overlaps with the low risk group in terms of OS. With regards to PFS, both indexes are poor at separating low and intermediate risk groups. In summary, both indexes are good at defining a relatively small high-risk population but do not accurately segregate the rest. FLIPI2 does not appear to be superior to FLIPI for risk stratification. This supports that the future lies in uncovering biological factors that might help in the guidance of treatment, in addition to segregating patients more accurately into specific risk groups.

Gribben:Roche: Honoraria; Genentech: Honoraria; GSK: Honoraria; Muundipharma: Honoraria. Montoto:Genentech: Research Funding; Roche: Honoraria.