https://www.ajmc.com/journals/evidence-based-oncology/2018/june-2018/medical-world-news-clinical-updates
Medical World News: Clinical Updates

Coverage by Jaime Rosenberg and Laura Joszt

New Test Could Make Multiple Myeloma Diagnosis as Easy as Drawing a Blood Sample

One day, multiple myeloma may be diagnosed without subjecting patients to a painful bone biopsy, according to research on a new blood test published in Integrative Biology.

For the last 10 years, researchers at Kansas University (KU) have been developing a blood-based test for a variety of cancer diagnoses, including multiple myeloma. The blood test uses a small plastic chip that delivers the same diagnostic information through a simple blood draw.

“We’ll be able to eliminate the need for bone-marrow biopsies and allow the clinician to determine the best way to treat the disease using a blood draw,” Steven Soper, PhD, foundation distinguished professor of Chemistry and Mechanical Engineering at KU and a member of The University of Kansas Cancer Center, said in a statement.2 “From this test, the clinician will be able to determine the stage of the disease, what type of drug will best treat the disease, and monitor for signs of recurrence if the disease goes into remission.”

The new chip improves accuracy over previous chips developed to test for multiple myeloma, according to the researchers. Previous chips picked up regular blood cells instead of multiple myeloma cells. The chip test from KU identified circulating plasma cells in all patients with smouldering and symptomatic multiple myeloma, 78% of patients with monoclonal gammopathy of undetermined significance (a precursor to multiple myeloma), and none of the control patients.

The chip is also cheaper than previous versions and can be produced for a couple of dollars per unit, according to Soper, who led the research.

The goal, he said, is that screening for cancer will one day be routine and widespread so there can be a diagnosis long before symptoms present themselves. He added that integrating the test into care can be as easy as screening blood drawn during an annual physical for cancer.

The new test for multiple myeloma will be brought to market by BioFluidica. The technology is already being tested at Children’s Mercy Hospital in Kansas City on pediatric patients with acute leukemia, Soper explained. The test is being used to identify tumor cells in blood to see signs of disease recurrence.

“We’ve demonstrated the utility of this technology in a variety of cancer diseases,” Soper said. “Here, we’re homing in on multiple myeloma, but we’ve developed tests for 2 forms of leukemia and for pancreatic cancer, prostate cancer, ovarian cancer, colorectal cancer, and breast cancer. With our technology, we’ll be able to see if patients are developing cancers before they have overt symptoms and help improve survival.”

References
  1. Kamande JW, Lindell MAM, Witek MA, Voorhees PM, Soper SA. Isolation of circulating plasma cells from blood of patients diagnosed with clonal plasma cell disorders using cell selection microfluidics. Integr Bio (Camb). 2018;10(2):82-91. doi: 10.1039/c7ib00183e.
  2. Chip-based blood test for multiple myeloma could make bone biopsies a relic of the past [press release]. Lawrence, KS; The University of Kansas; April 16, 2018. news.ku.edu/2018/04/16/chip-based-blood-test-multi- ple-myeloma-could-help-make-bone-biopsies-relic. Accessed May 1, 2018.



Novel Drug Shows Promise in Acute Myeloid Leukemia by Suppressing 2 Proteins

The first in a new class of anticancer agents has shown promise against acute myeloid leukemia (AML), according to findings published in Science Translational Medicine.1 The findings led to a phase 1/2 clinical trial for patients with advanced AML and advanced myelodysplastic syndrome.

The research, from investigators at Albert Einstein College of Medicine, describes how an experimental drug, ALRN-6924, targets p53, a protein that is inactivated in AML. The drug inhibits the proteins MDMX and MDM2, both of which inactivate p53 when they are overexpressed. When p53 is activated, it suppresses tumors.

In preclinical studies, ALRN-6924 tripled the median AML survival rate in mice transplanted with human leukemia cells from 50 days to approximately 150 days.

“This is a very striking response,” study leader Ulrich Steidl, MD, PhD, professor of cell biology and of medicine and the Diane and Arthur B. Belfer Faculty Scholar in Cancer Research at Einstein and associate chair for translational research in oncology at Montefiore Health System, said in a statement.2“Most experimental drugs for leukemia achieve an increase in survival of only a few days in these preclinical models. Even more importantly, ALRN-6924 effectively cured about 40% of the treated mice, meaning they were disease free more than 1 year after treatment—essentially a lifetime for a mouse.”

AML is an often-lethal cancer, with only 27% of people who are diagnosed surviving for 5 or more years. Furthermore, in the past half century, the outcomes for AML have not significantly improved, according to a press release from Albert Einstein College of Medicine.

The research found that not only did ALRN-6924 block interaction of both MDMX and MDM2 with p53 in more mature AML cells, but the effect was also seen in the immature stem cells that produce AML cells.

“This is important because AML is driven by stem cells—and if you don’t target stem cells, the disease will come back very quickly,” Steidl said.

He added that some other cancers driven by overexpression of MDMX and MDM2 and inactivation of p53, such as some forms of breast cancer and lung cancer, could be treated with ALR-6924.

References
  1. Carvajal LA, Ben Neriah D, Senecal A, et al. Dual inhibition of MDMX and MDM2 as a therapeutic strategy in leukemia [published online April 11, 2018]. Sci Transl Med. doi: 10.1126/scitranslmed.aao3003.
  2. Novel drug shows promise against acute myeloid leukemia [press release]. Bronx, NY: Einstein Medical Center; April 11, 2018. einstein.yu.edu/news/releases/1292/novel-drug-shows-promise-against-acute-myeloid-leuke- mia/. Accessed May 1, 2018.
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