Wednesday, December 29, 2010

About FLIPI in Follicular Lymphoma

Currently, the standard method for determining the prognosis of follicular lymphoma, and separating low-risk patients (who can delay treatment) from high-risk patients (who may require immediate treatment), is a tool called the Follicular Lymphoma International Prognostic Index (FLIPI).

How FLIPI Works


FLIPI was established in a 2004 article published in Blood, with a large list of European and American co-authors. It identified five risk factors associated with a poorer prognosis (lower survival rates) for follicular lymphoma. Patients get one "point" for each risk factor they carry; essentially, the more points a person accumulates, the more dangerous their disease is:


  1. Age (over 60 years)
  2. Elevated LDH level
  3. Advanced Disease (Stage III or Stage IV)
  4. Low hemoglobin level
  5. Five or more affected groups of lymph nodes

Patients with 0 or 1 risk factor are considered low-risk. (Most patients present with advanced disease, and therefore have at least 1 risk factor.) Patients with 2 risk factors are considered medium-risk. Patients with 3-5 risk factors are considered high risk. As a general rule, high-risk patients will benefit more from early treatment, whereas patients at lower risk are better candidates for "watch & wait" (W&W), at least initially.


Problems with FLIPI


FLIPI is a product of its time. When it was first developed, it estimated a 5-year survival time of about 90% for low-risk patients, 70% for medium-risk patients, and 52% for high-risk patients, and 10-year survival times of 70%, 50%, and 35%, respectively. These spreads were wide enough apart to provide considerable utility -- but they were based on CHOP-centered treatment. Since the introduction of rituximab, there is convincing evidence that survival rates for follicular lymphoma are changing. This means that the survival rates predicted by FLIPI are now highly inaccurate. Several recent review articles have suggested that the 5-year survival rates even for Stage IV patients may be as high as 90%-95%.

The heart of the problem is that modern treatments are highly effective in patients who typically rack up multiple scores on FLIPI (e.g. for advanced disease). Other advanced new therapies may also be coming online in the next several years. Some treatments may be effective enough, against even high-risk patients, that different risk factors must be identified. Efforts to develop a revised FLIPI are ongoing, and briefly discussed below.


How FLIPI Relates to Other Risk Assessment Tools

You are likely to come across at least two other risk assessment tools in the context of follicular lymphoma. The first is the International Prognostic Index (IPI). The IPI actually precedes the FLIPI, and was intended to apply to all lymphomas. It also has five risk factors: age (60+), advanced disease (Stage III or Stage IV), elevated LDH levels, poor performance status, and multiple disease sites out of the lymph node system.

The second tool is a newer index, the Second Follicular Lymphoma International Prognostic Index (FLIPI-2). FLIPI-2 is intended to solve some of the problems inherent in the original FLIPI, discussed above -- in particular, the rapid increase in survival times following the introduction of rituximab and another targeted therapies. FLIPI-2 identifies a different set of risk factors and, at least for the moment, is based on progression-free survival rather than overall survival. FLIPI-2's risk factors are age (60+), bone marrow involvement, low hemoglobin count, elevated beat2-microglobulin count, and bulky disease (defined in that study as a lymph node greater than 6 cm long).

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