Follicular lymphoma (FL) accounts for 10% to 20% of all newly diagnosed non-Hodgkin lymphomas, making it one of the most common subtypes of lymphoma. Although considered incurable, advances in treatment have drastically increased the overall survival for patients, with many patients having very long-term survival after diagnosis. Treatment advances, combined with a better understanding of disease characteristics, offer promise in the search for a cure for this disease.

In a review article published in The Cancer Journal, Stefano Luminar, MD, from the department of surgical, medical, and dental sciences related to transplant, oncology, and regenerative medicine at the University of Modena and Reggio Emilia in Italy, and colleagues examined how far treatment has come, limitations to choosing the right treatment, and where the management of FL is heading. Overall survival for advanced disease is near 90%, and the median overall survival (OS) is around 20 years; however, relapse remains a major concern for long-term survival.

By better understanding prognostic indicators, clinicians can identify patients more likely to relapse. These indicators can also guide decisions for initial treatment, maintenance therapy, and relapse treatment. “[E]fforts to identify these patients at high risk of early treatment failure have become a key research priority in the field,” wrote the investigators.

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Staging and Prognosis

FL is typically an indolent disease that responds well to initial treatment but has a known risk of relapse. A powerful prognostic factor, staging is a key component in determining therapeutic direction. In addition, several other clinical characteristics at diagnosis hold prognostic significance.

Bone marrow biopsy and positron emission tomography (PET) frequently demonstrate advanced FL at presentation, with about 10% to 15% of patients having localized disease that often responds well to curative c. About 20% to 25% have advanced, asymptomatic, and low-volume disease that does not necessitate immediate treatment. These patients are monitored until a clear disease progression is observed. Most patients (60% to 70%) have advanced disease or high tumor burden at diagnosis, requiring systemic treatment.

Several indices stratify patients into low-risk and high-risk groups with differences in OS and progression-free survival (PFS) based on clinical features of the disease. The most common index is the Follicular Lymphoma International Prognostic Index (FLIPI). This defines 5 clinical factors:

  • More than 4 nodal areas
  • A greater than normal level of serum lactate dehydrogenase (LDH)
  • Age older than 60 years
  • Advanced stage disease
  • Hemoglobin less than 120 g/L

The FLIPI2 index adds bone marrow involvement, node diameter, and B2 microglobulin (B2M) as additional prognostic factors. The most recent index from the PRIMA trial ( Identifier: NCT00140582) uses only bone marrow biopsy and B2M greater than normal.

Progress in next-generation sequencing also adds to risk stratification. When gene expression profiling was conducted using information from patients in the PRIMA study, an expression-based predictor of PFS was created using 23 genes. Validated in 3 independent groups, the gene expression profiling was able to predict PFS independent of maintenance therapy and FLIPI tools. Future gene-expression profiling tools must be more readily available and tested in larger cohort studies in order to demonstrate validity.

Response to first-line treatment as measured by PET scans may also help predict outcomes. The authors noted a review study that found that fewer patients who were postinduction PET-positive after initial treatment remained progression-free at 4 years than those with a PET negative scan.