Prognostic Value Of GELF Criteria and FLIPI2 For Newly Diagnosed Follicular Lymphoma Receiving R-CHOP Chemotherapy
Authors: Murakami Satsuki , Kato Harumi , Yamamoto Kazuhito , Taji Hirofumi , Hirano Daiki , Yatabe Yasushi , Nakamura Shigeo , Kinoshita Tomohiro 
Published: October 2019

Abstract
Follicular lymphoma (FL) is the most frequent low-grade lymphoma and survival duration is heterogeneous. Follicular lymphoma international prognostic index 2 (FLIPI2) is a useful prognostic tool for the identification of patients with FL at different risk in the rituximab era. On the other hand, Groupe d’Etude des Lymphomas Folliculaires (GELF) criteria is defined for patients in whom immediate therapy is necessary. In this study, we determined the value of FLIPI2 and GELF criteria as prognostic tools for follicular lymphoma.
Among 181 consecutive FL patients newly diagnosed in our institute from 2000 to 2011, data of FLIPI2 and GELF criteria were available for 147 patients. Of the 147 patients, a total of 102 patients were diagnosed as clinical stage II to IV and received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) based chemotherapy. The remaining 45 patients were treated with CHOP like regimens or other treatment modalities. Of the 102 patients who had rituximab usage, 2 patients (2%) received rituximab maintenance therapy. Detailed patients characteristics were shown in Table 1. Survival analysis was carried out using the Kaplan–Meier product-limit method.Table 1Baseline patients’ characteristics (stage ≥II, received R-CHOP)ALL (n=102)Cross-validation cohort (n=65)n (%)n (%)Sex (Male)45 (44)33 (51)Median age (range)58.5 (39-84)58 (39-79)Age (>60)38 (37)24 (37)ECOG PS (>1)2 (2)1 (2)Stage ≥III85 (83)52 (80)Bulky (≥7 cm)19 (19)13 (20)Serum LDH level (>normal)29 (28)19(28)Histology (Grade1/2/3)15/74/1110/46/8FLIPI2Low17 (17)14 (22)Intermediate58 (57)38 (58)High27 (26)13 (20)GELF criteria (High)56 (55)32 (49)Rituximab maintenance2(2)1(2)
First, we performed analysis using 102 patients who were diagnosed as clinical stage II to IV and received R-CHOP based chemotherapy. With a median follow-up of 6.3 years (range: 0.7-14.0 years), the 6-year overall (OS) and progression-free survival rates (PFS) of the 102 patients were 89% (95%CI: 78 to 98) and 62% (95%CI: 51 to 71), respectively. According to FLIPI2, three risk groups (low risk, intermediate risk and poor risk) were separated in OS analysis. Estimated 6-year OS rates in patients with high and low tumor burden defined by GELF were 82% and 98%, respectively (P=0.02, Log-rank). PFS rates of patients with high tumor burden defined by GELF criteria were worse compared to those with low tumor burden (53% vs. 72%, p=0.02, Log-rank). When we divided patients into two group using both FLIPI2 and GELF criteria (FLIPI2-GELF combined model), patients, who had high tumor burden defined by GELF criteria and who were classified intermediate risk or poor risk group defined by FLIPI2 (FLIPI2-GELF high) showed worse OS rates compared to the remaining (FLIPI2-GELF low) patients (83% vs. 95%, p=0.03, Log-rank). Patients with FLIPI2-GELF high also represented worse PFS rates compared to FLIPI2-GELF low patients (51% vs. 72%, p<0.01, Log-rank). The results suggested that FLIPI2-GELF combined model could more precisely separate patients into each risk group.
For validation, we next performed cross-validation analysis using 65 patients who were diagnosed as clinical stage II to IV and received R-CHOP based chemotherapy. The patients were selected from the first cohort of 102 cases (Table 1). With a median follow-up of 6.2 years (range: 0.7-14.0 years), estimated 6-year OS rates in patients with high and low tumor burden defined by GELF were 80% and 97%, respectively (P=0.03, Log-rank). Estimated 6-year PFS rates in patients with high and low tumor burden defined by GELF were 51% and 66%, respectively (P=0.12, Log-rank). Using FLIPI2-GELF combined model, estimated 6-year OS rates in patients with FLIPI2-GELF high and low were 78% and 97%, respectively (P=0.02, Log-rank). Estimated 6-year PFS rates in patients with FLIPI2-GELF high and low were 47% and 68%, respectively (P=0.04, Log-rank). In 147 cases treated with R-CHOP, CHOP based regimens,or other treatment modalities, FLIPI2-GELF combined model also could divide the two group in OS (p=0.01) and PFS (p<0.01) analyses.
In conclusion, we confirmed GELF criteria could be used for reproducible prognostic tool for newly diagnosed follicular lymphoma receiving R-CHOP based chemotherapy. GELF criteria combined with FLIPI2 might be a more precise and repeatable prognostic indicator for survival after first-line therapy in patients with follicular lymphoma.

Disclosures:
No relevant conflicts of interest to declare.