Treatment Strategies in Follicular Lymphomas: Current Status and Future Perspectives

Abstract

Although little progress has been made in the treatment of follicular lymphomas (FL) within the last few decades, several new therapeutic modalities have recently demonstrated promising activity. These include myeloablative therapy followed by autologous stem cell transplantation in younger patients in first remission revealing a significant prolongation of remission duration in three prospective randomized trials, whereas the impact on overall survival still needs to be determined. Adding the anti-CD20 antibody rituximab to conventional chemotherapy resulted in a significant increase in remission rate, remission duration and in two of four currently available prospective randomized studies even in a longer overall survival. A prolongation of remission duration was also seen when rituximab was administered as maintenance after cytoreductive therapy or by prolonged application as a single agent. Radioimmunotherapy (RIT) with radioisotopes coupled to monoclonal antibodies revealed encouraging data in several phase II studies. Prospective randomized studies are warranted, however, to define the impact of RIT on FL therapy. New therapeutic perspectives also emerge from increasing insights into the biology of the disease that unravel molecular targets for novel agents, some of which have entered clinical evaluation already.

Preclinical and clinical evaluation of epratuzumab (anti-CD22 IgG) in B-cell malignancies

“…Relatively few patients with early-stage disease are treated with external beam radiotherapy, and can expect to enjoy a significant long-term disease-free survival. However, most patients have advanced-stage disease at diagnosis, and historically options have included careful observation ('watch and wait') as well as alkylating agents and purine analogues as single-agents or in combination (Gallagher et al, 1986;Hiddemann et al, 2005;Zinzani, 2005). Median survival has been previously reported to be in the range of 8-10 years (Gallagher et al, 1986;Hiddemann et al, 2005).…”

“…However, most patients have advanced-stage disease at diagnosis, and historically options have included careful observation ('watch and wait') as well as alkylating agents and purine analogues as single-agents or in combination (Gallagher et al, 1986;Hiddemann et al, 2005;Zinzani, 2005). Median survival has been previously reported to be in the range of 8-10 years (Gallagher et al, 1986;Hiddemann et al, 2005). Other treatment modalities have been explored, including high-dose chemotherapy and autologous stem cell transplantation (AuSCT), and more recently both unlabeled and radiolabeled monoclonal antibodies directed against CD20 have become part of standard regimens (Hiddemann et al, 2005).…”

“…Median survival has been previously reported to be in the range of 8-10 years (Gallagher et al, 1986;Hiddemann et al, 2005). Other treatment modalities have been explored, including high-dose chemotherapy and autologous stem cell transplantation (AuSCT), and more recently both unlabeled and radiolabeled monoclonal antibodies directed against CD20 have become part of standard regimens (Hiddemann et al, 2005).…”

Pathway-specific apoptotic gene expression profiling in chronic lymphocytic leukemia and follicular lymphoma

“…1,3,4 Despite recent developments in various biological therapies, these tumors remain largely incurable. 5,6 The pathogenesis of both chronic lymphocytic leukemia and follicular lymphoma is incompletely understood, but multiple defects in the apoptotic pathway have been identified. In follicular lymphoma, overexpression of BCL2 as a result of the t(14;18) cytogenetic abnormality is one of the best characterized mechanisms by which apoptosis is inhibited in follicular lymphoma.…”

Efficacy and safety of the combination of rituximab, fludarabine, and mitoxantrone for rituximab‐naive, recurrent/refractory follicular non‐Hodgkin lymphoma with high tumor burden

“…Recently, investigators demonstrated that the addition of the humanized anti-CD20 antibody rituximab to a first-line chemotherapy regimen improved outcome. [1][2][3][4] However, most patients who receive rituximab-containing regimens eventually will develop recurrent disease.…”