Circulating Tumor DNA Measurement in Lymphoma One of the Big Stories From ASH

As I write this column, I am attending the 64th American Society of Hematology (ASH) Annual Meeting and Exposition. As is always the case, there are more big stories of amazing progress in the field of hematology and oncology than I can possibly summarize in one short column. One of these, which I have written about before and will probably write about again, is the emergence of bispecific antibodies to redirect native T lymphocytes against malignant B lymphocytes. But in this column I’ll focus on a different and perhaps equally important story—namely, that measurement of circulating tumor DNA (ctDNA) can be used to predict outcomes and assess responses to treatment of various lymphomas.

Detection of microscopic amounts of measurable residual disease (MRD) is not entirely a new story in hematology. At this ASH meeting, we are now seeing firm evidence that MRD testing with novel technologies can be used in a variety of ways in lymphomas. First, higher baseline levels of ctDNA correlate with adverse outcomes in patients with both aggressive non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma. Second, failure of MRD to become undetectable during and after therapy for aggressive NHL, mantle cell lymphoma, and Hodgkin lymphoma predicts a higher likelihood of recurrence. Third, when used at the end of treatment in aggressive lymphoma, a specific test used to measure ctDNA called PhasED-Seq was superior to PET/CT scans, the conventional method of assessing response to therapy in aggressive lymphomas, at predicting which patients would and would not relapse.

One can imagine using MRD results during treatment to tailor therapy for individual patients. Can patients who achieve undetectable MRD during therapy have their therapy shortened or reduced? Should patients who do not achieve undetectable MRD during or after therapy have their therapy intensified? Can we omit scans in patients whose MRD tests become negative after therapy, thereby reducing cost and exposure to potentially harmful radiation? I would advise that we not jump to conclusions and think we know the answers to these questions without controlled clinical trials. For example, in a mantle cell lymphoma study, patients with undetectable MRD still benefited from maintenance rituximab (Rituxan) as opposed to stopping treatment. Not all MRD tests are created equal, so the characteristics of the tests will need to be considered when designing trials to act on MRD results.