Haematological Malignancies
Novel Therapy of Relapsed and Refractory Classical Hodgkin’s Lymphoma Enrico Derenzini,1
Daniela Buglio1 and Anas Younes2 1. Postdoctoral Fellow; 2. Professor, Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center
Abstract
Classical Hodgkin’s lymphoma (HL) is generally considered a highly curable disease, with approximately 80 % of patients cured with standard first-line chemotherapy. The standard treatment approach for relapsed/refractory patients is second-line salvage chemotherapy followed by autologous stem cell transplantation (ASCT). About half of all patients undergoing ASCT are rescued and definitely cured by such an approach, but the outcome in patients relapsing or refractory to second-line chemotherapy and ASCT is dismal, with a median survival of less than three years. Therapeutic options for this subset of patients comprise tandem ASCT, reduced-intensity allogeneic stem cell transplantation (allo-SCT) and novel agents. Median overall and progression-free survival rates following allo-SCT have ranged from 27 to 56 % and from 18 to 39 %, respectively, with a treatment-related mortality ranging from 15 to 25 %. Several new compounds have been identified as promising agents for the treatment of patients with relapsed classical HL. These drugs have shown promising activity in a subset of heavily pre-treated relapsed/refractory patients, with response rates and disease control rates exceeding 40 and 70 %. If approved, these compounds will probably change the standard of care, making it possible to develop combination regimens with chemotherapy or other new agents, thus improving efficacy with a decreased toxicity profile.
Keywords
Hodgkin’s lymphoma, panobinostat, SGN35, rituximab, everolimus, daclizumab, autologous stem cell transplantation, allogeneic stem cell transplantation
Disclosure: The authors have no conflicts of interest to declare. Received: 20 September 2010 Accepted: 4 August 2011 Citation: European Oncology & Haematology, 2011;7(3):203–10 Correspondence: Anas Younes, Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009, US. E:
ayounes@mdanderson.org
Although Hodgkin’s lymphoma (HL) is considered one of the most curable human cancers, the treatment of patients with relapsed and refractory disease, especially those who relapse after autologous stem cell transplantation (ASCT), remains challenging.1,2
Furthermore, because the median age of patients is in the mid-30s, the impact of early mortality on the number of years lost from productive life is remarkable. At the present time, patients with HL whose disease relapses after stem cell transplantation have no curative options. New drugs and novel treatment strategies that are based on our understanding of the disease biology and signalling pathways are needed to improve treatment outcomes in these patients. Ironically, because HL is a rare disease and has long been considered highly curable, the search for new therapies and treatment approaches has grown slowly in the past, with no new drugs approved in the last 30 years.
With recent advances in our understanding of HL pathology, biology and immunology, several therapeutic targets have been identified and are currently under preclinical and clinical investigation. Some of these new compounds have already been evaluated in large Phase II clinical trials seeking potential approval by regulatory agencies. This article focuses on current treatment strategies for patients with relapsed and refractory HL, including the role of stem cell transplantation and promising new monoclonal antibodies and small molecules.
© TOUCH BRIEFINGS 2011
Role of Stem Cell Transplantation Autologous Stem Cell Transplantation
About half of all patients undergoing ASCT are rescued and definitely cured by such an approach, but the outcome in patients relapsing or refractory to second-line chemotherapy and ASCT is dismal, with a median survival of less than three years.5
The superiority of high-dose chemotherapy with stem cell rescue over standard second-line chemotherapy alone was demonstrated in two randomised trials.3,4
The
need to identify patients who will not benefit from ASCT has resulted in a large number of studies describing various prognostic factors, including stage and time to relapse, B symptoms, extranodal disease, bone marrow involvement and chemosensitivity at relapse. Depending on the presence or absence of these factors, progression-free survival (PFS) and overall survival (OS) rates range from 10 to 83 % and from 13 to 90 %, respectively (see Table 1).6–12
So, the ideal patient who will
benefit from ASCT is the one with limited stage, long time to relapse and chemosensitive disease, while the patient with advanced stage, short time to relapse and refractory disease has the worst prognosis. A recent report13
on the role of tandem ASCT suggests a potential OS and PFS benefit for poor-risk patients – with reported five-year PFS and OS of 36 and 45 %, respectively, in patients resistant to second-line chemotherapy – and these results compare favourably with other published series of patients refractory to second-line chemotherapy.12
One of the most important and widely accepted prognostic factors for patients undergoing ASCT appears to be chemosensitivity at relapse,
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