Prognostic indicators

Follicular Lymphoma International Prognostic Index (FLIPI)

  • When using the International Prognostic Index (IPI) (see DLBCL prognostic indicators section), only 10% to 15% of patients with follicular lymphoma are classified in the poor-risk category, which may not accurately reflect the true nature of the disease. Thus, the IPI was considered to be less than optimal for identifying patients in whom intensive therapy must be tested21
  • To account for this deficiency, an international cooperative study was designed, and the FLIPI was published in 200421
  • The FLIPI predicts the risk of disease recurrence and overall treatment outcome through 5 adverse prognostic risk factors and stratifies patients into 3 risk groups21 (Tables 5 and 6)

Table 5. Follicular Lymphoma International Prognostic Index (FLIPI) risk factors

Table 5. Follicular Lymphoma International Prognostic Index (FLIPI) risk factors.21

Table 6. The Follicular Lymphoma International Prognostic Index (FLIPI) prognostic index by risk group

Table 6. The Follicular Lymphoma International Prognostic Index (FLIPI) prognostic index by risk group.21

  • This widely accepted prognostic index is based on a retrospective analysis of more than 4000 patients diagnosed with fNHL between 1985 and 199221
    • The analysis showed that patients falling into the low-risk group had a median 10-year overall survival (OS) rate of 71% vs 36% for patients falling into the high-risk group21 (Table 6 and Figure 1)
  • While the primary endpoint for the study was OS, the FLIPI is also considered to be highly predictive of progression-free survival (PFS)22
    • The FLIPI may be used in determining patient prognosis, but it has not been established as a means of selecting treatment options outside of the clinical trial setting10

Figure 1. Overall survival of fNHL patients by FLIPI risk group

Figure 1. Overall survival of fNHL patients by FLIPI risk group.21

FLIPI2

  • Because FLIPI was based on a retrospective analysis that was formulated before the widespread use of chemoimmunotherapy, the prospective F2 trial (N=1093) was designed and conducted23
  • In the F2 trial, PFS was the primary endpoint instead of OS due to the lengthy course of the disease23
  • Following analysis of the F2 trial, 3 prognostic risk factors changed23 (Table 7)
    • The FLIPI prognostic factors that were removed for the FLIPI2 included Ann Arbor stage III/IV, number of nodal areas >4, and LDH level >upper limit of normal (ULN)
    • The prognostic factors that were added for the FLIPI2 include longest diameter of the largest involved node (LoDLIN) >6 cm, serum B2M >ULN, and bone marrow involvement23
  • The analysis showed that patients in the low-risk group had a 5-year PFS rate of 80% vs 19% for patients in the high-risk group23 (Table 8)

Table 7. The 5 revised adverse prognostic risk factors for the FLIPI2

Table 7. The 5 revised adverse prognostic risk factors for the FLIPI2.23

Table 8. The FLIPI2 prognostic index by risk group

Table 8. The FLIPI2 prognostic index by risk group.23

  • The relatively small size of the F2 trial and the newness of these data have resulted in a slow uptake of this new prognostic tool. However, current studies have shown that the FLIPI2 is a reproducible prognostic index of clinical utility for the initial prognostic assessment of patients with fNHL24

Gene expression profiling (GEP) and prognosis

  • GEP has shown that there are 2 distinct patterns of gene expression that can differentiate between a disease that is generally indolent in nature (present in three-fourths of patients with follicular lymphoma) and one that is more aggressive. The median OS of patients with the indolent form of disease as characterized by GEP is 11.1 years. The median OS of the aggressive type of follicular lymphoma is 3.9 years7,25
  • The lymphoma microenvironment has been characterized using GEP to assess the nature of infiltrating immune cells in diseased tissue7
    • Expression data have identified 2 immune response signatures, immune response-1 (IR-1) and immune response-2 (IR-2)7,25,26
      • IR-1 suggests the involvement of T cells and monocytes and predicts a favorable prognosis25
      • IR-2 indicates the involvement of cells such as monocytes and dendritic cells and suggests a poor outcome25
    • In fNHL tumors that express both signatures, the relative ratio of expression level between IR-1 and IR-2 may be an important predictor of the length of survival25
  • Interactions between malignant cells and the lymphoma microenvironment may be clinically relevant, because survival was found to be associated with the nature of the tumor-infiltrating immune cells25
  • The characterization of the lymphoma microenvironment, such as in the identification of gene signatures from the infiltration of immune cells, is a promising area of research25

View References for this site section