High throughput flow cytometry-based drug sensitivity testing for melflufen in multiple myeloma
Huppunen, Maiju-Emilia (2020-09-04)
Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
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Multiple myeloma (MM) is a hematological plasma cell malignancy in the bone marrow. Lately, increased knowledge of MM pathogenesis and advances in therapy have improved the survival of MM patients. However, due to the unique and complex genome of each patient, some patients are resistant to standard therapies while others achieve durable response but eventually experience relapse. Therefore, new strategies especially for relapsed and refractory and high-risk multiple myeloma (RRMM, HRMM) patients, who have poor response to current therapies, are required. Melflufen, a novel prodrug of the alkylating agent melphalan, has shown significantly decreased resistance effects and more selective cytotoxicity compared to melphalan in vitro and in vivo, but the molecular markers identifying the sensitive subgroups of MM patients have not yet been discovered. The aim of this study was to identify a melflufen-sensitive subgroup of MM patients by utilizing a high throughput flow cytometry-based drug sensitivity testing platform. For the assessment, mononuclear cells from bone marrow of MM patients were derived and melflufen sensitivity of different cell populations tested. As a result, malignant plasma cells were significantly more sensitive to melflufen than to melphalan. Importantly, all MM patient samples including RRMM and HRMM patients were sensitive to melflufen although to varying degrees suggesting these patients may benefit from melflufen treatment. Further integration of the results with additional molecular information may lead to discovery of new biomarkers and thus the prediction of melflufen responses can result in more effective disease management and save patients from ineffective therapies.