Follicular Lymphoma

From Diagnosis to Treatment Options

Explore the complexities of Follicular Lymphoma, the most common indolent B-cell lymphoproliferative disorder

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Variable Progression

Progression and Survival

Follicular Lymphoma (FL) is the most prevalent indolent B-cell lymphoproliferative disorder of malignant germinal follicular center B cells, characterized by a slow progression and a variable clinical course. Diagnosis typically involves histological examination through a biopsy of a lymph node or another affected tissue.

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FL Stages

A Closer Look

Clinical manifestations of FL in Class 1-2 and 3A include inertia, while Class 3B presents with invasion similar to diffuse large B-cell lymphoma (DLBCL).

FL can be categorized into three stages

Stage 1

0 to 5 matricytes per high-power field

Stage 2

6 to 15 matricytes per high-power field

Stage 3

More than 15 matricytes per high-power field

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Statistical Uncertainty

By The Numbers


Median age at diagnosis is 60 years


Median overall survival is more than 15 years


20% relapse within 2 years after 1L treatment


10% may transform over their lifetime


14,000 FL patients in the US annually


Indolent yet incurable disease


Some subsets exhibit significantly worse prognosis.


Roles of epigenetic modifiers and survival pathways are poorly understood


Unknown disease progression for patients


Most receive generic therapy irrespective of prognostic scores


~80% of FL mono-therapies are also approved for other B-cell lymphomas


Restricted precision medicine options in FL

Disease Challenges

Heterogeneity Drivers Unknown

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Treatment Options

Therapeutic Approaches

The selection of a specific treatment regimen depends on factors like the disease stage, patient co-morbidities, and the preferences of the physician and patient. Treatment selection lacks any markers identified as ancillary or surrogate for heightened risk of transformation. It's worth noting that a minority of patients may be "cured" after front-line therapy.

FDA Approved Treatments

Initial Observation

Radiation Therapy

Monoclonal Antibody & Immunotherapy

Bi-Specific T Cell Engager Immunotherapy

Chimeric Antigen T Cell Cellular Therapy

Targeted Therapies

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Unmet Needs

Addressing FL's Unmet Needs

Understanding Tumor Heterogeneity

The challenge in effectively treating Follicular Lymphoma (FL) lies in Identifying and understanding the cellular and molecular determinants of tumor heterogeneity driving FL progression, treatment resistance, and transformation. Drivers of FL heterogenous evolution remain unclear and key biological questions need to be answered.

Key Biological Questions

How can we identify the cancer progenitor cell (CPC) responsible for relapse and/or resistance to current treatments, and what is its co-dependence with the tumor microenvironment (TME)?

What clinical strategies can be developed to target the CPCs, potentially through designing new screens for ad hoc drugs and immunotherapies?

Can existing drugs be targeted early enough to effectively avoid or contain the relapse of Follicular Lymphoma?

Enhancing Diagnostic and Monitoring Tools

Identifying and validating surrogate or ancillary biomarkers to predict disease progression and transformation is crucial. These biomarkers help inform treatment selection, enable response monitoring, and reduce the duration of ineffective therapies.

Overcoming Treatment Challenges

Developing innovations for FL in the private sector is challenging due to the disease's indolent nature and low incidence. The long outcome endpoints, modest incidence, and generally favorable survival rates do not drive strong interest or commitment among drug developers. Addressing the unbalanced risk/reward ratio is necessary to motivate further innovation.

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