Hodgkin’s Lymphoma: An Environmental Scan
Table of Contents
4.2 Targeted Therapies
Research activity into the development of new drugs for use in treating HL is a priority and reiterated in a recent publication from the German Study Group (Böll, Borchmann, and Diehl 2010). In considering all HL patients, who have undergone treatment for HL and the specific group that experiences a relapse subsequent to first-line interventions, new drug therapies are required to continue to reduce the burden of illness suffered as a result of the toxicity from conventional chemotherapy and radiation treatments along with offering patients experiencing a relapse additional treatment options. The development of specific biomarkers for targeted therapy could largely impact the 15-20% of individuals with early stages and approximately 30% with advanced stage who relapse after primary treatment (Persky 2007).
The median age of diagnosis for HL is 35 years. Given, the increased risk associated with standard conventional treatments, it is paramount to continue to investigate and understand pathways of treatment that use less toxic pharmacological agents along with developing therapies such as molecular targeting in order to progress to more personalized treatments for individual patients. The biochemical details of emerging therapies including; monoclonal antibodies, CD30, CD20, CD40, CD80 and VEGF; bispecific constructs; immunotherapy and pharmacologic inhibitors are far beyond the scope of this report; however informative information is available through the publications of the German Research Group and a detailed summary found with the following citation (Böll, Borchmann, and Diehl 2010).
In general, the benefit of monoclonal antibodies is that they can provide a way to destroy the cancer cell without systemically attacking otherwise healthy cells as demonstrated in gold-standard treatments. This is important for HL patients, one there are substantial late effects from the gold-standard treatments, targeted therapies such as immunotoxins are designed not to affect the body systemically; therefore, patients and particularly younger HL patients can have their overall quality of life improved by reducing the secondary effects of treatment (Küppers, Yahalom, and Josting 2006). Second, there are a sub-group of individuals who do not respond to the gold-standard, primary level treatments and as such, targeted therapies can provide an additional treatment option if first line options fail. Finally, there is disagreement among clinicians whether or not patients presenting in the early stages of cHL require radiation therapy, again reducing the patient’s exposure to toxic therapies by offering alternative therapies such as targeted treatments can largely reduce the late effects.
Researchers and clinicians working with monoclonal antibodies are focused on developing very specific antibodies, targeted to each of the HL tumor sub-types in the hope of replacing more systemic treatments with targeted therapies as a primary approach to treating HL. Once such monoclonal antibody, Rituximab has been used and despite the success of Rituximab for many patients with B-lymphocyte cancers, a percentage of patients either become resistant to this treatment thus, there is a need for research to expand the effectiveness of monoclonal antibodies. In HL, the composition of the tumor including finding abnormalities such as the RS cells is in fact quite rare (approximately 1-2% of the total tumor mass) thus, the study of the impact of molecular entities specifically designed to treat HL has not developed (Van Vlierberghe et al. 2009).
As noted, the International Prognostic Score is used to assess the level of risk a patient has at the time of diagnosis in how they will fair in treatment for HL. However, the current model of assessing risk cannot predict which patients will fail in treatment nor does it render any information on how a patient would do in treatment under-going a stem-cell transplant. Therefore, biomarkers are essential to have as new and additional pieces information to predict not only risk but overall survival. Further research is required in the area of biomarkers relevant to each sub-type of HL; however, “clinically relevant biomarkers have not been established to improve on the International Prognostic Score” (Steidl et. all, 2010. Abstract).
As mentioned, isolating particular RS cells in a HL cancer tumor is difficult as they are found in such few numbers. The number of RS cells found in HL tumors is very low; therefore, advancements in isolating and understanding the molecular structure and characteristics of the RS cell is progressing but at a slow rate. “The search for clinical and biological prognostic or risk scores that help in identifying patients at high risk for primary refractory disease or relapse has been only partially successful so far” (Böll, Borchmann, and Diehl 2010). Furthermore, there is considerable disparity across patients and sub-types of HL surrounding the number of RS in a tumor (Steidl et al. 2010). Although studies have examined the biomarkers of the RS cells more investigation is necessary, thereby improving the ability to not only assess risk but to do so for special patient populations (Sánchez-Espiridión et al. 2009) (Staege et al. 2008). Being able to identify those with a higher risk of poor prognostic outcomes would improve overall survival and treatment outcomes in HL and possible impact rates of toxicity and late effects of conventional therapy (Steidl et al. 2010).
Suggestions include more collaborative work on an international level in order to combine knowledge and use resources and available data more efficiently in order to create new therapies. This will require larger scale studies, international partnerships and dedicated funding to create the scientific environment where advancements in the understanding of biomarkers and resulting treatments specific to particular patient pathologies can happen. Developments in this area will impact the overall production of ‘personalized therapies’, which will help all cancer patients and specifically HL patients while simultaneously offer new and different treatments for patients who experience a relapse of their disease or build up an immunity to currently available chemotherapy drugs (Savoldo et al. 2007). Of course, the hope is to advance in this area whereby personalized therapy is available to all cancer patients but of particular importance are those patients who have already tried drugs that are available and such pharmacological agents do not work or only work for a period of time.