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Lymphoma – personalised medicine

Personalised medicine – identifying the best treatment for the individual patient – is not new, but its role in healthcare is rapidly increasing.

The aim of personalised medicine is to optimise outcomes by integrating information on tumour biology (obtained through genomics technologies) with clinical information, and tailoring therapy.

Better knowledge of a cancer’s molecular biology means clinicians can increasingly tell the many biologic differences between individual patients’ cancers, and a greater ability to measure biologic characteristics helps point to the use of a specific, or targeted drug.

In lymphoma, many treatment options available, and knowing more about the different subtypes enables the most effective treatment to be selected for each patient. 

Personalised medicine and lymphoma

Clinical practice for lymphoma has relied on treatment algorithms (a best practice approach to medical treatment) to provide similar treatments to large subgroups of patients. Now, clinicians realise unique biologic differences exist among the different subtypes of lymphomas and between individuals with the same subtype.

In diffuse large B-cell lymphoma (DLBCL) – the most common form of aggressive non-Hodgkin lymphoma – gene expression profiling has identified two main biologic subtypes – activated B-cell-like (ABC) and germinal centre B-cell-like (GCB), and 85% of patients with DLBCL have either ABC or GCB subtypes.

Most people with DLBCL are treated in a similar way, regardless of subtype, but this information will become more relevant soon as there are drugs in development that are expected to benefit one subtype or the other, such as ibrutinib, a selective, irreversible inhibitor of Bruton’s tyrosine kinase that is typically expressed in the ABC subtype.

Another example is double hit lymphoma. These patients have two genetic abnormalities and it’s important that they are appropriately identified as they typically do not do well with the present standard treatment for DLBCL.

Is gene expression profiling for everyone? 

Most treatment decisions in lymphoma are still not based on a patient’s genetic profile, and gene expression profiling isn’t routine care for all patients. There are some simple immunohistochemistry tests that can help identify people with ABC or GCB DLBCL, but these techniques are not perfect and there is debate about whether these tests should be done.

As more is learned about the biology of the different lymphomas and as more selective treatments are developed, tools to measure genetic differences will need to become routinely available.

Benefits of personalised medicine

Being smarter in choosing the best drug for an individual patient means providing the optimal treatment, with the highest chance of helping the patient and sparing them the unnecessary toxicity of a drug that is not likely to work. Newer, more targeted therapies are likely to be expensive, so it is imperative that they are given to patients who will benefit.

Changes in drug development

Whereas chemotherapy has a broad mechanism of action, most drugs in development are ‘targeted therapies’ with a known specific mode of action that is efficacious for certain cancers. And, as the design of most drugs in development is based on genetic differences and abnormalities, clinical trials have biologic questions built into them to test whether patients have those biologic features.