Trial Information

F2-PROTOCOL: Prospective Collection of Data of Possible Prognostic Relevance in Patients With Follicular Lymphoma

So far, in patients with lymphoma a variety of studies aimed at the evaluation of prognosis
have been conducted. In particular, different demographic, clinical and biological factors
have shown a prognostic role in univariate and multivariate analysis, including age, gender,
stage, tumor burden, bone marrow involvement, systemic symptoms, Performance status, serum
lactate dehydrogenase (LDH) level, anemia, erythrocyte sedimentation rate (ESR) and beta-2
microglobulin.

The combination of those parameters has allowed the identification of several prognostic
scores.

Attempts to define prognosis in follicular lymphomas begun in the late '70s. Then, when in
1993 the International Prognostic Index (IPI) was defined for aggressive lymphomas it was
also applied to low-grade lymphomas leading to conflicting results, and the need for a
prognostic index specifically designed for follicular lymphomas emerged.

A large study on prognosis in patients with follicular lymphoma was performed by the Italian
Lymphoma Intergroup that leaded to the definition of the Italian Lymphoma Intergroup (ILI)
score, based on 987 patients (Federico M et al. Blood 2000; 95(3):783-789). In 2004 the
Follicular Lymphoma International Prognostic Project allowed the definition of a new score
on 4167 pts with follicular lymphoma, the Follicular Lymphoma International Prognostic Index
(FLIPI) (Solal-Céligny P et al. Blood 2004;104(5):1258-1265). This score is based on the
evaluation of age (younger than 60 years vs 60 years or older), Ann Arbor stage (I-II vs
III-IV), number of nodal sites (0-4 vs > 5 or more), Hemoglobin (Hb)level (greater than or
equal 12g/dL vs lower than 12g/dL), serum Lactate Dehydrogenase (LDH) (normal vs elevated)
and identifies three main groups of patients with different survival:low risk (0-1 factors);
intermediate risk (2 factors); high risk (3-5 factors).

Notwithstanding the huge number of patients considered in these studies, all mentioned
prognostic scores (IPI, ILI and FLIPI) are based on a retrospective analysis of archive
data. This approach can introduce biases that can hamper final results. A first problem is
the selection of patients that can be influenced by single institution policy and patient's
or physician's related factors. Furthermore, some important variables, such as
beta2-microglobulin or Erythrocyte Sedimentation Rate (ESR), that have frequently shown a
high prognostic significance in univariate analysis, are hardly included in the final
indexes because they are available only in a small number of patients thus loosing their
value in multivariate analysis. Then, lacking homogeneous and prospectively defined
criteria, retrospective evaluation of some study parameter as for example clinical response
cannot be easily defined and all derived endpoints such as Failure Free Survival (FFS)or
Progression Free Survival (PFS) may be biased.

Finally the results of a retrospective analysis aiming at the evaluation of survival are
dependent on the type of administered treatment and with the recent advent of new drugs such
as monoclonal antibodies and purine analogs that can be used also in the elderly patients
the role of some established prognostic factor may have changed.

These are the reasons why we thought it would be useful to start a new study based on the
prospective registration in a short period of time of patients with follicular lymphoma for
whom it would be possible collect an exhaustive set of clinical data and biological
information.