Haematological Malignancies
Current First-line and Salvage Treatment Strategies in Patients with Advanced-stage Follicular Lymphoma
Frank Heinzelmann,1 Michael Bamberg2 and Martin Weinmann3
1. Radiation Oncology Specialist; 2. Medical Director; 3. Vice Director and Leading Senior Physician, Department of Radiation Oncology, University of Tübingen
Abstract
In patients with advanced-stage follicular lymphoma (FL) there are many treatment options available. Besides watchful waiting in asymptomatic patients, current first-line treatment strategies include rituximab ± single-agent chemotherapy, chemoimmunotherapy and radioimmunotherapy. In case of relapse, the use of chemoimmunotherapy, radioimmunotherapy and autologous haematopoietic stem cell transplantation (HSCT) results in enhanced response rates, progression-free survival (PFS) and overall survival (OS) compared with chemotherapy alone. However, long-term results are marred by high relapse rates and the risk of secondary malignancies after autologous HSCT. To date, in patients with relapsed/chemoresistant disease, myeloablative/reduced intensity conditioning protocols in combination with allogeneic HSCT presumably constitute the only curative approach but are associated with high treatment-related mortality. Although advances in supportive care have resulted in improved outcomes, reliable strategies for adequate patient selection are mandatory. In the palliative setting, low-dose involved-field irradiation constitutes an effective treatment option in order to control local symptoms with potential long-lasting response.
Keywords
Advanced-stage follicular lymphoma, chemoimmunotherapy, radioimmunotherapy, radiotherapy, autologous transplantation, myeloablative conditioning, reduced intensity conditioning, allogeneic transplantation
Disclosure: The authors have no conflicts of interest to declare. Received: 13 July 2010 Accepted: 19 August 2010 Citation: European Oncology, 2010;6(2):58–63 Correspondence: Frank Heinzelmann, University of Tübingen, Department of Radiation Oncology, Hoppe-Seyler-Str 3, 72076 Tübingen, Germany. E:
frank.heinzelmann@med.uni-tuebingen.de
Follicular lymphoma (FL) is the second most common subtype of non- Hodgkin lymphoma worldwide in adults (~20–25%). The origin of FL cells is follicle centre B lymphocytes. In the majority of patients the disease is diagnosed in advanced stages III/IV (~80%). For asymptomatic patients, watchful waiting may be appropriate since deferred therapy tested in three randomised trials showed no detrimental effect on cause-specific or overall survival (OS)1–3 regression has been reported.4
and a substantial rate of spontaneous In case of symptomatic disease, patients
require systemic therapy. The exploration of different chemotherapy regimens that provide initially high response rates (75–90%)5–7
did
not lead to a significant improvement of long-term prognosis. The median survival time was over three decades in a range between eight and 10 years.8
More recently, a significant prolongation of overall survival was reported due to the introduction of novel therapeutic strategies such as chemoimmunotherapy, radioimmunotherapy and use of autologous/allogeneic haematopoietic stem cell transplantation. This article will discuss the different treatment approaches, addressing the issues of current first-line and salvage strategies in patients with advanced-stage FL.
First-line Treatment Strategies in Advanced-stage Follicular Lymphoma In recent years, promising first-line treatment approaches have been developed in patients with advanced-stage FL. The implementation of the monoclonal anti-CD20 antibody rituximab has demonstrated
58
In order to prevent relapses, the concept of rituximab maintenance therapy following first-line induction with various chemoimmunotherapy regimens is currently under evaluation in international phase III randomised trials such as the Primary Rituximab Maintenance (PRIMA) study. The first interim analysis of the PRIMA study compared two years of rituximab maintenance therapy versus observation in FL patients responding to first-line immunochemotherapy with either eight cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) (75%), rituximab, cyclophosphamide, vincristine and prednisone (R-CVP) (22%) or rituximab, fludarabine, cyclophosphamide and mitoxantrone (R-FCM) (3%). After a median follow-up of 25 months, the PRIMA study demonstrated a significant improvement of two-year PFS (rituximab maintenance 82% versus observation 66%; p
© TOUCH BRIEFINGS 2010
efficacy with an excellent toxicity profile. Binding of rituximab to the CD20 surface antigen, which is expressed by more than 90% of follicular lymphoma cells, leads to complement-mediated lysis and cell-mediated cytotoxicity and induces apoptosis. Rituximab has been successfully applied as a single agent9,10
and in combination
with different chemotherapy regimens (chemoimmunotherapy). Chemoimmunotherapy enhanced response rates and significantly improved progression-free survival (PFS) and overall survival (OS) when compared with chemotherapy alone (see Table 1).11–15
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