Ask the Doctor: How can biomarker testing help DLBCL patients?

The emergence of biomarking testing has provided new insights into the molecular and genetic underpinnings of many types of cancer as well as differences in an individual patient’s cancer at the molecular level. These differences, or alterations (also known as mutations or biomarkers), can help physicians facilitate the delivery of the right treatment to the right patient at the right time.

Such testing has been used for several subtypes of lymphomas, including, diffuse large B-cell lymphoma (DLBCL). Mark Roschewski, MD of the National Institute of Health, answered questions regarding transformed and relapsed DLBCL, and how biomarker testing can be helpful to patients.

If my DLBCL is transformed from Follicular, does this alter treatment or prognosis?

It depends on the details. In general, transformed lymphomas have more underlying genetic complexity and in some cases are more resistant to standard anthracycline-based chemotherapy. However, many cases can do well with standard therapy and we do not have good biomarkers to identify these patients. In particular, patients who have not had any treatment seem to fare better than those who have histologic transformation after multiple lines of treatment. Overall, we do consider the prognosis worse, but the data is not definitive. At our institution, we usually add targeted agents to chemotherapy backbones and we are studying this approach in an upcoming clinical trial. One of the most important differences, however, is that the risk of relapse includes both follicular lymphoma and diffuse large B-cell lymphoma, so the clinical monitoring after treatment must be indefinite.

What are biomarkers and how do they help in diagnosing lymphoma?

A biomarker is a biologic feature of the tumor and they can be diagnostic or predictive biomarkers that predict response to a specific treatment. We have many examples of diagnostic biomarkers that help make the diagnosis of lymphoma subtypes. For example, the expression of CD10, BCL6, and MUM1 can be used as biomarkers that subdivide diffuse large B-cell lymphoma (DLBLC) into molecular subtypes. Often when we speak about biomarkers, we mean predictive biomarkers that can identify patients most likely to respond to a specific treatment. For example, if we think patients with DLBCL are most likely to respond to a BTK inhibitor if they are CD10-negative, then that because a very useful biomarker. The challenge with biomarkers is the need for validations in large cohorts to become actionable across the spectrum of disease. This last step can be challenging due to the complexity of lymphoma.

I was initially diagnosed with DLBCL 6 years ago. With new diagnostic procedures, should my disease be reevaluated at any point to look for genetic markers?

For patients with a history of DLBCL and no evidence of relapse, there is no need to test the tumor or look for any germline (inherited) genetic markers except in very specific circumstances. If the disease has relapsed, then it is important to get a repeat biopsy and apply modern techniques to understand the biology of the relapsed tumor as it often has important differences.