Deeper Responses Push Importance of MRD Testing to Surface
Pediatric acute lymphoblastic leukemia (ALL) is considered by some to be “one of the most dramatic cancer success stories”.1 In the last five decades, the five-year relative survival rate in pediatric ALL has increased by more than 89 percent – from just 3 percent in 1964 to more than 90 percent in 2010 (Figure 12-4).
The rapid improvement in pediatric ALL began with the introduction of combination chemotherapy in the mid-1960s, with the rate of response and depth of that response further increasing with the development of multi-drug regimens and the introduction of bone marrow transplants. Still, the five-year survival rate in the 1980s lingered around 73 percent and relapse remained a significant issue even after successful therapy.5
It was at this time that physicians looking to further improve patient outcomes and reduce recurrence of ALL started exploring methods to detect the tiny amounts of cancer remaining after therapy but undetectable by traditional imaging and laboratory methods – minimal residual disease (MRD).6 Thanks to the efforts of many, several techniques for MRD detection and quantification have been developed, testing is now considered standard of care, and treatment can be adjusted based on MRD results in order to get the cures we’re all after.
Today, thanks to novel therapies and new treatment regimens, other blood cancers are experiencing the kind of advances that were seen in pediatric ALL. Multiple myeloma patients, for example, are achieving depths of response unseen even a few years ago. In chronic lymphocytic leukemia (CLL) too, dramatic improvements in the efficacy of treatments have led to progressively higher percentages of clinical complete remissions.
With the advances across blood cancers, it is once again time to look to MRD testing to help push responses farther. The field’s recognition of this is evident from the growing discussion of the role of MRD in clinical practice and drug trials that can be found in the published literature and the proceedings of medical meetings. For example, in the last 10 years, the number of abstracts mentioning MRD presented at the American Society of Hematology (ASH) Annual Meeting has increased threefold – from just 79 abstracts in 2005 to more than 230 in 2015 (Figure 2).
The Food and Drug Administration and many pharmaceutical and biotechnology companies are exploring the potential of MRD as a primary endpoint in clinical trials, a move that could have important implications for drug development – something we are also actively studying. With each new study the value of MRD detection continues to be established.
Adaptive Biotechnologies and its collaborators are presenting 10 studies about MRD in lymphoid cancers at this year’s ASH Annual Meeting. Read more here.
1Kersey JH. Fifty years of studies of the biology and therapy of childhood leukemia. Blood. 1997;90(11):4243–51.
2Facts 2014-2015. Leukemia and Lymphoma Society; 2015.
3Zuelzer WW. Implications of long-term survivals in acute stem cell leukemia of childhood treated with composite cyclic therapy. Blood.1964;24:477-494.
4SEER (Surveillance, Epidemiology and End Results) Cancer Statistics Review, 1975-2011. National Cancer Institute; 2014.
5Kersey JH. Fifty years of studies of the biology and therapy of childhood leukemia. Blood. 1997;90(11):4243–51.
6Hansen-Hagge TE, Yokota S, Bartram CR. Detection of minimal residual disease in acute lymphoblastic leukemia by in vitro amplification of rearranged T-cell receptor delta chain sequences. Blood. 1989;74(5):1762-67.