Focus on Personalised Medicine
While the term personalised medicine is about 15 years old, it is starting to play a bigger role in how healthcare is practised. However, when it comes to defining what is meant by personalised medicine, it is not so straightforward.
The definition has evolved over the years and will likely continue to do so as medicine advances. Currently, most would see it as an approach to providing healthcare that involves integrating information on tumour biology obtained through genomics technologies together with clinical information in order to tailor therapy and optimize outcomes.
Personalised medicine refers to a practice of medicine that tries to identify the best treatment for the individual patient. Given the growing knowledge about a cancer’s molecular biology, clinicians are now starting to be able to distinguish an increasing array of biologic differences between individual patient’s cancers. As well, there is a greater ability to measure biologic characteristics that are unique to the patient that would then argue for the use of a specific, or targeted drug. For example in lymphoma, there are multiple treatment options available and knowledge about the different subtypes is growing, enabling selection of the most effective treatment for each patient.
Role of personalised medicine in lymphoma
Within lymphoma, clinical practice has historically relied on treatment algorithms aimed to provide similar treatments to large subgroups of patients. However, clinicians are starting to recognise that there are unique biologic differences among the different subtypes of lymphomas, and between individual patients with the same lymphoma subtype. An example of this is diffuse large B-cell lymphoma (DLBCL), the most common form of aggressive non-Hodgkin lymphoma. Through gene expression profiling, two main biologic subtypes have been identified within DLBCL, namely activated B-cell-like (ABC) and germinal centre B-cell-like (GCB). Approximately 85 per cent of patients diagnosed with DLBCL can be categorised as having either ABC or GCB subtypes. Currently, most patients with DLBCL are treated in a similar fashion, regardless of subtype. However, this information will become more relevant in the near future as there are drugs in development that are expected to benefit one subtype versus the other, such as ibrutinib, a selective, irreversible inhibitor of Bruton’s tyrosine kinase which is typically expressed in the ABC subtype.
“In a study recently presented at the ASH annual meeting, the drug ibrutinib was shown to almost exclusively benefit patients with the ABC subtype of diffuse large B-cell lymphoma. This provides an important example of why genomic information will become more important as these targeted agents become available” said Dr. Laurie Sehn. Dr. Sehn is Chair of the British Columbia Cancer Agency Lymphoma Tumour Group as well as Clinical Associate Professor at the University of British Columbia, Vancouver, Canada. She is also Chair of the Lymphoma Coalition (LC) Medical Advisory Board.
Another example of where personalised medicine will play a key role is in patients who have double-hit lymphoma. These are patients who have two genetic abnormalities (MYC and BCL2 translocations) within their cancer. While it is estimated that patients with this abnormality make up less than 5 per cent of the DLBCL population, it is important they are appropriately identified as they typically do not do well with the present standard treatment.
Gene expression profiling for everyone?
Within routine care, gene expression profiling is not currently done in all patients. However, there are simple immunohistochemistry tests that pathologists can perform to help identify, for example, if patients have ABC or GCB DLBCL. These techniques, however, are not perfect and there is debate as to whether these tests should be done. Currently, most treatment decisions in lymphoma are not based on a patient’s genetic profile. As more is learned about the biology of the different lymphomas and as more selective treatments are developed, it will become necessary for the tools to measure genetic differences to be made routinely available.
Likely benefits of personalised medicine
The goal of personalised medicine is to select the most effective treatment for a patient’s cancer.
“If we can get smarter about choosing the best drug for the individual patient, it would allow us to provide the optimal treatment with the highest likelihood of helping the patient, while at the same time, sparing them the unnecessary toxicity of a drug that is unlikely to work,” said Dr. Sehn.
In addition, as some of the newer and more targeted therapies are likely to be expensive, it is even more imperative that they are given to patients who will benefit.
Patient role in personalised medicine
Patients need to make the effort to be as well informed as possible about their lymphoma. It is important to realise that not all lymphomas are the same and that there are treatment options specific to their lymphoma subtype that they need to ask their physician about. Patients should also ask their physician if there are additional pathology tests that can be undertaken to ensure that their subtype is clearly defined in order to determine the best treatment path.
Physician role in personalised medicine
Understanding lymphoma subtypes and being informed about developments in specialty testing procedures will be key. Dialogue between clinicians and specialty pathologists needs to improve. If tests are not being done at a treatment centre that would allow a physician to select a more specific treatment for a patient, the clinician needs to have access to pathologists who can ensure the tests are undertaken.
Changes in drug development
In the past, chemotherapy was viewed as having a relatively broad mechanism of action. Now, drugs are more often referred to as targeted therapies because most in development have a specific mode of action so it is known exactly what the drug does and in what kind of cancer it is likely to be efficacious. The majority of drugs in development have been designed based on the growing understanding of genetic differences and abnormalities between cancers. In addition, clinical trials have biologic questions built into them and part of the drug development process revolves around trying to test whether patients have those biologic features.
As these more targeted drugs come to market, it will be imperative to have a system in place that allows for specific biologic information to be measured, such that the drugs can be administered to the appropriate patients. Given the anticipated expense of some of the newer targeted therapies, medical budgets will be challenged to pay for them and, consequently, the question arises as to who will pay for the diagnostic test? Ideally, the drug, along with a reliable commercially available diagnostic test should be provided and approved as one package, eliminating concerns as to who pays for it. This is an area that LC will examine further.
“Personalised medicine is not going away. We are quickly moving into an era where medicine will rely on detailed biologic information and this is where lymphoma treatment is going as well,” said Dr. Sehn.
Currently, personalised medicine is still a relatively new field so it’s not possible to provide definitive information as to how it will affect patients and their disease. However, as information becomes available, LC will keep you informed.
For more information on personalised medicine, talk to your doctor and you may find the following websites useful:
The European Personalised Medicine Association http://epemed.alwaysdata.net/index.php
Personalized Medicine Coalition (USA) http://www.personalizedmedicinecoalition.org/