A wide of range of Myeloma therapies are currently available for patients at diagnosis and relapse. The drugs may be grouped according to their class of action – immunomodulatory drugs, Imids (such as thalidomide and Lenolidomide), proteasome inhibitors, PI (Carfilzomib, Bortezomib) and monoclonal antibodies, Mab (Daratumamab, Elotuzamab). Currently, several other drugs with different mechanisms of action are also in clinical trials. The toxicity profile of a number of these drugs is a major limiting factor in both choice at relapse and ongoing therapy.
Two drug classes are associated with significant cardiothrombotic toxicity. Particularly high rates of venous thromboembolism are seen with Imids whilst cardiovascular toxicity (pulmonary hypertension and cardiac failure) is more common with PI such as Carfilzomib. Neurotoxicity is also more common with Imids particularly with Thalidomide. There are several new markers of endovascular damage such as microvesicles and several plasma/serum biomarkers of potential interest for measuring toxicity. We propose to evaluate microvesicles, using an in vitro model and potential serum/plasma biomarkers for neurotoxicity and cardiothrombotic toxicity