Exploring the impact of the diffuse large B-cell component in untreated follicular lymphoma

Naveed Saleh, MD, MS, for MDLinx | May 25, 2018

Outcomes for patients diagnosed with the follicular lymphoma/diffuse large B-cell lymphoma component (FL/DLBC) are no worse than the clinical outcomes of DLBCL alone, according to a new study published in the Annals of Oncology.

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Follicular lymphoma typically has an indolent clinical course with continual relapses and lengthened survival.

“The aim of the present study was to analyze the clinicobiological characteristics, treatment, response, and outcome of patients diagnosed with FL/DLBCL in a single institution,” wrote the authors, led by Laura Carola Magnano, Department of Hematology, Hospital Clinic, Institut d’investigacions Biom?diques August Pi i Sunyer, Barcelona, Spain. “We also compared the outcome of FL/DLBCL patients with that of patients diagnosed with pure FL or de novo DLBCL during the same period of time.”

The researchers chose to include patients from a single institution to limit bias.

FL typically has an indolent clinical course with continual relapses and lengthened survival. A small number of patients progress from FL to DLBCL, a more aggressive lymphoma with poor prognosis.

Although FL/DLBCL typically crops up during the progression of FL, a substantial DLBCL component is evident at the initial FL diagnosis some patients. Genetic alterations such as TP53 and mutations such as NOTCH have been implicated in this transformation.

This coexistence on examination of a biopsy specimen (ie, FL/DLBCL) has been alternatively called either “early transformation” or “composite lymphoma.”

Clinicians treat this transformed lymphoma with aggressive lymphoma-type immunochemotherapy that is usually followed by intensification with autogeneic stem cell transplantation (ASCT) if the clinical response is favorable and the patient is in good condition. This approach is used to treat FL/DLBCL despite a paucity of research on the topic.

In this study, the research team included a total of 878 patients diagnosed with FL 1, 2, or 3a (n=320); FL 3b (n=8); DLBCL (n=510); and FL/DLBCL (n=40) that were all diagnosed at the same institution between 2002 and 2015. All patients were treated in the rituximab era, and the only inclusion criterion was the existence of histological specimens.

“The definition of FL/DLBCL was based on the presence of a variable DLBCL component in the lymph node biopsy of a patient otherwise diagnosed with FL,” wrote the authors. “According to WHO recommendations, the DLBCL component was defined as an area of large cells in sheets lacking follicular architecture assessed by staining for follicular dendritic cells (CD21 or CD23).”

They found that the proportion of the DLBCL component was highly variable. The cell-of-origin (COO) was germinal center B-cell like DLBCL (GCB DLBCL) in 86% of patients, activated B-cell like DLBCL (ABC DLBCL) in 10% of patients, and unclassified in 4%. Furthermore, NOTCH1/2 were mutated in 10% of FL/DLBCL cases.

“Interestingly, COO had prognostic impact in FL/DLBCL patients showing that GCB subtype had better outcome than ABC,” wrote the authors. “These findings are important as they suggest that treatment might be tailored to underlying biology in order to reverse the adverse outcome associated with ABC phenotype.”

The researchers found that the proportional DLBCL component had no effect on overall survival (OS). Moreover, they found that FL/DLBCL histology did not rise to the level of independent prognostic value for OS, as determined by multivariate analysis.

Some initial characteristics of FL/DLBCL were closer to FL, such as primary nodal origin and advanced stage, whereas others were intermediate. Patients with FL/DLBCL were treated in the same manner as patients with DLBCL—without intensification. The response rate in FL/DLBCL was comparable to that of DLBCL, but lower than the response rate observed in FL.

The authors conclude that although infrequent, the DLBCL component of FL should be diagnosed. These transformed lymphomas should be treated with immunochemotherapy; intensification appears unnecessary.

To read more about this study, click here

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