2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

KEY POINTS
Table 1. Clinical, Biologic, and Genetic Factors with Prognostic Value in Follicular Lymphoma*
Factor Clinical Impact Comment
Histopathologic features
Tumor grade Grade 1–2 is generally more indolent than grade 3 Reproducibility amongst pathologists can be low. Grade 3A is
treated similarly to grade 1–2. Grade 3B is treated similarly
to diffuse large B-cell lymphoma
Diffuse architecture Controversial Increased areas of diffuse architecture may increase risk of
transformation
Proliferation rate
Clinical indices
Controversial
IPI Worsening survival with high scores Unable to distinguish prognosis amongst vast majority of
patients who have low IPI scores
FLIPI 1 Worsening survival with high scores Analysis was done in a pre-rituximab population. Primary end
point was overall survival.
FLIPI 2
Blood markers
Worsening PFS with high scores Analysis was done in patients receiving immunochemotherapy.
Primary end point was PFS.
Lactate dehydrogenase Decreased survival with elevated values Part of IPI and FLIPI-1
Beta-2 microglobulin Shorter FFP and decreased survival with elevated
values
Part of FLIPI-2
VEGF, FGF, TNF, endostatin
Individual proteins or RNA
Shorter FL Small numbers of FL patients in most of these studies
BCL6, CD10, PU.1 Favorable
MCL1, MUM1, SOCS3, YY.1, BCLXL Gene expression profiling
Unfavorable
Immune response-1 and immune response-2 Immune response-1 has 9-fold more favorable
survival
81-gene predictor model
Microenvironment
Model was able to predict disease aggressiveness and disease
progression but was done in pre-rituximab era.
Macrophages Decreased survival
CD4� or CD8� T cells Controversial Conflicting reports in literature
T-regulatory cells
Molecular genetic biomarkers
Controversial Conflicting reports in literature
BCL2 Typically diagnostic and not prognostic. There may be differing prognostic implications of translocation
versus somatic mutations as source of BCL aberration.
MYC Worse prognosis Usually associated with transformation to high grade lymphoma.
TP53 Worse prognosis Associated with histologic transformation.
CCNB1 Improved survival
Abbreviations: FGF, fibroblast growth factor; FL, follicular lymphoma; FLIPI, Follicular Lymphoma International Prognostic Index; IPI, International Prognostic Index;
PFS, progression-free survival; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor.
* There is little consensus on the prognostic applicability of these biomarkers on an individual basis. Data abstracted from Relander T, Johnson NA, Farinha P, et al.
Prognostic factors in follicular lymphoma. J Clin Oncol. 2010;28:2902–2913.
● Follicular lymphoma is clinically and biologically
heterogeneous.
● There are currently few validated predictive or prognostic
tools available to guide treatment at an individual
level.
● Clinically, follicular lymphoma can be conceptualized
as a series of disease states with unique treatment
approaches and goals of treatment.
● Advances in the pathobiology of follicular lymphoma
have led to a new generation of agents that are now in
clinical trials.
● The optimal incorporation of these new agents will
likely build on existing treatment paradigms within
clinically distinct groups: treatment-naïve (low tumor
burden and high tumor burden), chemoimmunotherapy-sensitive,
and chemoimmunotherapy-resistant
disease.
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SONALI M. SMITH
FL. 8 Patients in the maintenance rituximab arm were
significantly less likely to require cytotoxic therapy at 3
years (91% vs. 48%; hazard ratio [HR] � 0.37; p � 0.001);
there was no improvement in overall survival, which was
95% in all arms. The Eastern Cooperative Oncology
Group (ECOG) RESORT (“Rituximab Extended Schedule
or Re-Treatment Trial”) trial sought to determine whether
a maintenance rituximab strategy following induction
rituximab could improve time to treatment failure compared
with a rituximab re-treatment strategy. 9 Although there
was no difference in the primary end point of time to
treatment failure (3.6 vs. 3.9 years for rituximab retreatment
vs. maintenance arms, respectively), significantly
fewer patients in the maintenance arm had not yet required
cytotoxic therapy at 3 years (HR � 2.5; p � 0.027). Should
rituximab induction plus maintenance replace “watch and
wait” as the initial management approach for low–tumor
burden and asymptomatic patients? This is clearly a matter
of debate, but highlights the interest and need to integrate
new agents in this clinical setting in which delayed time to
cytotoxic therapy could be a reasonable goal for some patients.