Follicular Lymphoma: The Management of Elderly Patient

Abstract

Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma, which typically affects mature adults and elderly, whose median age at diagnosis is 65 years. The natural history of FL appears to have been favorably impacted by the introduction of Rituximab. Randomized clinical trials demonstrated that the addition of rituximab to standard chemotherapy induction has improved the overall survival and new strategies of chemo-immunotherapy, such as Bendamustine combined with Rituximab, showed optimal results on response and reduced hematological toxicity, becoming one of the standard treatments, particularly in elderly patients. Moreover, maintenance therapy with Rituximab demonstrated improvement of progression-free survival. Despite these exciting results, FL is still an incurable disease. It remains a critical unmet clinical need finding new prognostic factors to identify poor outcome patients better, to reduce the risk of transformation and to explore new treatment strategies, especially for patients not candidate to intensive chemotherapy regimens, such as elderly patients. Some progress were already reached with novel agents, but larger and more validated studies are needed. Elderly patients are the largest portion of patients with FL and represent a subgroup with higher treatment difficulties, because of comorbidities and smaller spectrum for treatment choice. Further studies, focused on elderly follicular lymphoma patients, with their peculiar characteristics, are needed to define the best-tailored treatment at diagnosis and at the time of relapse in this setting.

MicroRNAs as Biomarkers of B-cell Lymphoma

“…However, nearly a third of patients with FL will suffer histologic transformation into a high-grade lymphoma often termed transformed FL (tFL), that is morphologically indistinguishable from DLBCL, with a much worse prognosis than the antecedent FL. 147,148 We identified a signature of 6 miRNAs ( miR-223, miR-217, miR-222, miR-221 , and let-7i and let-7b ) that could distinguish between de novo DLBCL and tFL. 50 Subsequently, miR-31 and miR-17-5p have also been identified as being differentially expressed between FL and tFL.…”

Identification of Recurrent Mutations in the microRNA-Binding Sites of B-Cell Lymphoma-Associated Genes in Follicular Lymphoma

“…BCL2 and EZH2 genes are both key genes in the pathogenesis of FL [ 20 , 26 , 27 ]. The t(14;18) translocation, present in >85% of FL cases, is considered the molecular hallmark of this disease and results in constitutive expression of the antiapoptotic protein BCL2 [ 28 , 29 , 30 ]. We observed that mutations in the BCL2 3´ UTR binding site for miR-5008 decreased the downregulation of this gene, thereby increasing BCL2 expression in luciferase assays, although we were not able to confirm this phenomenon in FL18 or U2932 cells, probably due to high basal levels of BCL2 expression in these t(14;18) cell lines.…”

Past, Present, and Future of Rituximab—The World’s First Oncology Monoclonal Antibody Therapy

“…Half of all FL patients are 60 or above, and treatment choices in these groups can be more difficult due to overall health and comorbidities. Still, the low toxic side effects of rituximab compared with chemotherapies indicate mAb as a safe and effective treatment in elderly FL patients both in combination or often as a monotherapy ( 47 ).…”