In today’s post, we discuss multiple myeloma and the proteasome inhibitors (bortezomib, carfilzomib and ixazomib), in particular. One of the ongoing debates concerns the toxicities and how the drugs in this class might differ. Whereas melphalan and the immunomodulatory drugs or IMiDs (lenalidomide, pomalidomide and thalidomide) have both been associated with secondary primary malignancies including AML and MDS, especially in combination, cardiotoxicity has been the main focus of debate for the proteasome inhibitors.
Is this a fair rap though?
We should remember that people with multiple myeloma typically tend to be around age 70. Think of Tom Brokaw, the famous newscaster, who was recently diagnosed with the condition aged 74 and is in the median age range, for example. In general, most people over 65 tend to have an increased incidence of cardiovascular disease and myeloma patients also tend to have a slightly higher risk due to disease factors, so there is a background effect that needs to be taken into account.
We should be mindful of the recent scare with cardiovascular events associated with ponatinib (Iclusig) in relapsed/refractory CML, which led to a temporary suspension from the US market and subsequent re-instation with a narrower license, appeared to unnerve both the FDA and investors alike.
At the American Society of Hematology (ASH) meeting in Decemeber, there were some interesting posters, presentations and debates on the proteasome inhibitors in myeloma that are worthy of further discussion. In addition, I sought some thought leader opinions and curated some of the interactions on this topic to add some colour commentary.