If you’ve been diagnosed with cancer, you probably want nothing more than to hear your oncologist use the word “remission”. It means that all signs and symptoms of the cancer have disappeared, at least by whatever test the doctor is using.1
For blood cancers like acute lymphoblastic leukemia (ALL), the technology often involves a microscope through which a pathologist looks for signs of cancerous cells.2
There are more precise methods that take advantage of modern molecular tools to detect minute amounts of cancer present at concentrations that less sensitive tests cannot detect.3 These tests for so-called minimal residual disease (MRD) have been shown to offer better assessments of drug response and relapse risk than standard techniques — and they may guide therapeutic decision-making in the future by identifying patients in need of further treatments or those who can be spared additional interventions.4
“By using molecular barcodes, we can peer deeper to find very small amounts of cancer that are still present,” said Dr. Gregory Friberg, vice president, global development at Amgen in Thousand Oaks, Calif. Researchers are exploring promising treatments that may impact what is already known about the presence of these residual cancer cells.
Yet, even though the science of MRD detection in blood cancers has been advancing for more than 20 years, the clinical application of MRD monitoring in ALL has only become widespread in the last decade.4,5
In part, that’s because it’s more technically challenging to test for cancer through genetic or biochemical means, as MRD detection requires, than it is with a microscope.5 “Very few centers are able to measure MRD, and few physicians are able to understand the implications of the test,” said Dr. Daniel DeAngelo, a hematologist at the Dana-Farber Cancer Institute in Boston, Mass.
Still, that’s no excuse not to make the technology more widely available and to improve awareness of what the test empowers physicians to do, he urged. “MRD needs to be part of the equation,” DeAngelo said.
MRD is usually evaluated in one of two ways, either through a technique called flow cytometry, which makes use of molecular cell markers to differentiate between normal and cancerous cells, or through DNA-based methods that can identify genetic alterations and over-expressed genes responsible for causing cancer.4 Either way, the tests can detect rare cancer cells lurking in the bone marrow or blood with a sensitivity of at least 1 in 10,000 — versus about 1 in 20 with a simple microscope exam.2,4
That’s important, said Dr. Friberg, because “we know that, if you can see the cancer, it’s still there — it’s hiding and it’s waiting to come back.”4
“If you can detect the cancer in 1 in 10,000 or even 1 in 100,000 cells,” he added, “the prognosis is absolutely going to be worse than someone in whom you can’t detect it.”2
As such, even though a patient who, after undergoing remission induction therapy and intensive consolidation therapy, may technically be classified as in clinical remission, if that patient still tests positive for MRD, then that patient has not achieved true molecular remission.2 That might mean additional rounds of chemotherapy or a stem cell transplantation.
But nowadays, there are immunotherapies that target proteins found on the surface of cancer cells, and that involve genetically engineering a patient’s own T cells to become cancer killers.6,7
The wealth of new therapeutic options makes it imperative — now more than ever — to enter the molecular era of diagnostic testing for blood cancers. “There are more arrows in the quiver,” Friberg said. This innovation also includes continued research with novel therapies being evaluated specifically with MRD diagnostics.5
In ALL, while MRD testing is most common in pediatric patients, it is also becoming more prevalent in adult patients as well.5 But, as DeAngelo, who specializes in treating adults with ALL, pointed out: “The biology probably dictates the outcome, not the age of the patient,” and so “MRD is likely just as important in adults as it is in kids.”8
According to DeAngelo, the value of MRD testing has been the subject of promising research in patients with multiple myeloma, as well as other hematological malignancies, including many common forms of lymphoma.9
Is it possible then to envision a future in which MRD testing becomes as routine as microscopy in the management of all blood cancers? “The field is moving in that direction now,” DeAngelo said.
1National Cancer Institute. Remission. https://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=45867. Accessed November 6, 2017.
2Gökbuget N, et al. Blood. 2012;120:1868-1876.
3Paeitta E. Bone Marrow Transplant. 2002;29:459-465.
4Brüggemann M, et al. Blood. 2012;120:4470-4481.
5van Dongen JJ, et al. Blood. 2015;125:3996-4009.
6Gökbuget N, et al. Blood Cancer J. 2016;6:e473.
7Sharpe M, et al. Dis Model Mech. 2015;8:337-350.
8Berry D, et al. JAMA Oncol. 2017; 3:e170580.
9van der Velden VH, et al. Leukemia. 2003;17:1013-1034.