High Level of CD71 Expression On Neoplastic B Cells At Diagnosis Is Predictive of Overall Survival After Rituximab and Anthracyclines Based Regimen in Follicular Lymphoma

The prognosis of follicular lymphoma (FL) remains a challenge despite stratification on the FLIPI scoring, histological grading, and microenvironement cell type infiltration. Thus, new biomarkers are needed to identify patients (pts) who require a more aggressive therapeutic strategy or targeted therapies. Transferrin receptor (TfR) is highly expressed in proliferating cells including non Hodgkin lymphoma cells. High TfR level has been associated with disease progression in chronic lymphocytic leukaemia and is observed at relapse in mantle cell lymphoma. Murine anti human TfR (CD71) antibody has been validated for histological and flow cytometric evaluation of TfR expression. The aim of this work was to assess expression and prognosis value of TfR expression on FL cells.

We retrospectively analyzed the expression level of CD71 in neoplastic B cells of FL lymph node biopsies at diagnosis of 45 pts who received first-line treatment with Rituximab and anthracyclines based chemotherapy at the hematology department of Necker Hospital, Paris, France, and assessed its prognosis value (second treatment free survival (TFS) and overall survival (OS)). High CD71 and Ki67 expression in FL lymph nodes biopsies were defined as upper than 25% of FL cells. CD71 expression was compared with FLIPI at diagnosis and the expression and prognosis value of Ki67 expression.

Characteristics of the cohort are shown in table 1. FLIPI risk was low in 7 pts (16%), intermediate in 19 (43%) and high in 18 (41%). FLIPI stratification did not show correlation with both OS and TFS in this small cohort of pts. Among 44 evaluable pts, CD71 expression was heterogeneous ranging from 0% to 90% of FL cells. T cell labeling was used as a quality control. CD71 low expression (²25% of tumor cells) was observed in 31 samples (69%) and KI67 low expression in 27 (60%). After a median follow-up of 40 months (range 1 – 94) for the all cohort, TFS was 68.9 % (95 % CI 0.55–0.82) and OS was 91.1% (95% CI 0.83 – 0.99). The mean TFS after R-chemotherapy was 86 months in the low CD71 level group vs. 18 months in the high CD71 level group (p=0,075). The mean estimated OS after first R-chemotherapy was 89 months in the low CD71 group vs. 54 months in the high CD71 group (p=0,006) (figure 1). By univariate analysis, high Ki67 expression was associated with significant lower OS (p=0.035) but not TFS (p=0,162). In multivariate analysis including CD71 level, FLIPI risk, FLIPI parameter groups, CD71 was the only factor independently associated with OS (p=0,019) and TFS (p=0,037). Furthermore, Cox regression analysis did not reveal any significant correlation between Ki67 and TFS or survival.

CD71 expression is an important independent histological prognostic factor in this monocentric retrospective study predicting OS in FL patients after first-line treatment with R anthracyclin based regimen. Ki 67 was also associated with OS in univariate analysis, but CD71 was the only independent factor associated with OS and TFS in multivariate analysis. These promising results warrant further studies in a larger prospective cohort and provide a rationale to target Tfr in relapsing refractory FL.

Figure 1:

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Overall survival (OS) after first line R anthracycline therapy according to the CD71 high and low risk groups

Figure 1:

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Overall survival (OS) after first line R anthracycline therapy according to the CD71 high and low risk groups

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No relevant conflicts of interest to declare.