Multiple myeloma is the next most common hematological malignancy and represents a continuous medical challenge since all patients eventually progress despite of many new drugs approved lately. The incidence of MM is about 6 to 8 out of 100.000 in Western Countries. APO010 (a hexameric FAS-ligand) is an immune-oncology drug, which mimics cytotoxic T-lymphocyte signaling to induce apoptosis and could therefore be a new effective drug for MM as these cells express CD95 (FAS-receptor).
Using a previously validated method by Medical Prognosis Institute A/S (MPI), we have developed an APO010 response predictor (APO010-DRPTM), which is based on gene expression cluster obtained by comparing associations between gene expression profiles and growth inhibition by APO010 in a panel of cell lines. A second step has included filtering the identified gene expression profile against mRNA expression from a collection of 3200 human tumors, thereby making a predictive profile for APO010 responsiveness. We have initiated to screen relapse/refractory MM patients by isolating CD138 positive myeloma cells from the bone marrow and perform APO010-DRPTM in order to select the patients with the highest likelihood of benefit from APO010 treatment.
Using the APO010-DRPTM analysis demonstrated multiple myeloma to be sensitive to APO010 compared to most solid tumors except breast cancer, which also appeared to be sensitive. First results from multiple myeloma patient screening will be presented at ESMO 2016.
Conclusion: Combining APO010 with DRPTM analysis will add a precision medicine element to immune-oncology treatment of multiple myeloma. This will enable us to identify patients with high likelihood of response and thereby facilitate focused future trial design and patient recruitment to achieve clinical success.
Clinical trial identification
Danish Ethical Committee, Journal nr.: H15018326, Approved on 01/03/2016
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All authors have declared no conflicts of interest.