Background: Multiple myeloma is a progressive malignancy of bone-marrow plasma cells, is currently incurable and has a 5 year survival rate of 43%. The global incident cases are 138 509 (in 2016), an increase of 126% since 1990. The three global regions with the highest incidence include Australasia, North America and Western Europe. For Australia, this translates to approx. 1500 diagnoses and 1 in 200 deaths annually.
Treatment typically involves high dose combination chemotherapy, but therapeutic response and patient survival are unpredictable and highly variable – attributed largely to the evolution of MDR in response to chemotherapy. The sooner that cancer cells evolving MDR can be detected, the sooner alternative treatment options can be initiated to prevent tumour re-occurrence and support quality of life. Currently, no procedures allow for a direct, non-invasive, continuous monitoring of MDR in this or any other cancer.
We have developed simple non-invasive test- a liquid biopsy- which provides a non-invasive, personalised test to support the routine monitoring of MDR in cancer patients. Essentially, the test scans a patient’s blood sample for a specific set of biomarkers, the evolution of which, correspond to disease progression and therapeutic response.
Results: The test monitors a patient’s unique cancer phenotype by analysing biomarker ‘signatures’ on extracellular vesicles (microparticles (MPs) 0.1 -1 um diameter), isolated from the blood samples of myeloma patients. The biomarker signatures include resistance markers, stem cell markers and phospholipid markers, the configuration of which correspond to disease progression and therapeutic response in individual patients. We describe MP subpopulations in the context of these signatures. We show that patients have higher P-glycoprotein (P-gp+) MPs in the total CD41a- and CD138-MP populations compared to healthy subjects. P-gp+MP levels correspond to poor treatment response and resistance to treatment. We also provide evidence for the presence of a ‘dual positive’ ‘stem cell-like’ subpopulation of CD138-P-gp+CD34+MPs in patients which are elevated in unresponsive disease and an evolving shift in the dominance of vesicle subtypes with disease progression and treatment failure.
Conclusions:We provide evidence that MDR in myeloma patients can be detected and monitored serially by analysing MPs in blood samples in the form of a ‘liquid biopsy’.This test has potential to complement existing biochemical benchmarks used in diagnosis and staging of myeloma. Our test enables a personalised approach to disease management with potential to improve treatment success and survival in myeloma patients
PCT/AU2018/050420 ‘Method for cancer prognosis’