The Follicular Lymphoma International Prognostic Index (FLIPI) Can Be a Useful Prognostic Indicator for Patients with Follicular Lymphoma Treated with Combination of Rituximab and Epratuzumab.

Abstract

Background: FLIPI has been proposed as an accurate, simple, and validated prognostic index on the basis of routinely performed tests (age > 60 yrs, Ann Arbor stage III-IV, serum LDH level increased, Hg < 12g/dL, and more than four nodal areas involved (Solal-Céligny et al., Blood 2004; 104: 1258–1265). FLIPI has reliably predicted outcome for many follicular lymphoma (FL) patients (pts) treated with chemotherapy and rituximab. Currently, monoclonal antibody (Mab) therapy and a number of radioimmunoconjugates are considered important components of the treatment of FL; therefore, evaluating FLIPI in clinical trials of these modalities is of interest for optimizing therapy.Methods: A subset analysis was performed to assess the impact of FLIPI on the outcome of patients with relapsed/refractory FL enrolled in a larger, multi-center, open label, single-arm study of epratuzumab (humanized anti-CD22 Mab) in combination with rituximab (chimeric anti-CD20 Mab) (Strauss et al., ASCO 2004).Results: A total of 32 pts with FL were treated according to this protocol (4 weekly infusions at full dose of each agent), including 16 pts who had received > 2 prior chemotherapy regimens and 11 pts who had previously received rituximab. Twenty pts (62%) achieved an objective response (OR), including 8 pts (25%) with complete responses (CR, CRu) and 12 (37%) with partial responses, with a median response duration of 16.5 months (95% CI: 6.3 - 25.4) and median time-to-progression (TTP) of 11 months (95% CI: 9.9 - 19.2).Conclusion: Our data indicate that high OR rates and durable CR/CRu's can be achieved with a combination of rituximab and epratuzumab in pts with low- (0–1) and intermediate-risk (2) FL, who failed multiple prior therapies. OR, CR rates and TTP are similar to rituximab front-line therapy for pts with low tumor burden FL (Solal-Céligny et al., Blood 104: 169a, 2004). The combination of rituximab and epratuzumab was significantly less efficacious for pts with high-risk (3–5) FLIPI (P=.0.0023 for TTP). This small Phase-II study supports the prognostic value of FLIPI for pts with recurrent FL who are treated with MAbs. Prospective use of FLIPI may facilitate the optimal design of randomized trials using rituximab in combination with epratuzumab in pts with FL.Results stratified by FLIPI risk groupsFLIPI score (No. of pts)OR (%)CR/CRu (%)Median Duration in months (95% CI)Median TTP in months (95% CI)TTP P-value*0–1 (11)9 (82)4 (36)15.7 (N/A)19.2 (10.3 – 21.3)0.00232 (9)6 (67)3 (33)18.3 (17.2 – 25.4)18.8 (10 – 26.7)3–5 (12)5 (42)1 (8)6.3 (N/A)7.7 (7.1 – 10.2)N/A - Not available due to patients with long TTPs that are still censored (i.e. not reached progression of disease). * - Patients with high (3–5) FLIPI scores versus others, based on the log-rank test.