Proteasome Inhibitor Use in Myeloma

Transcript:Heinz Ludwig, MD: So, the question is, what is the difference between the three proteasome inhibitors: carfilzomib, bortezomib, and ixazomib? They are somehow different in the mode of activity and certainly in the tolerance spectrum. NINLARO is exceptional because it’s extremely well-tolerated, does not induce or cause neuropathy, and has almost no cardiotoxicity or renal toxicity. Actually, when you use ixazomib in your patients, you are surprised about the excellent tolerance. Bortezomib is a very good drug. It’s the first proteasome inhibitor, but has the risk of neuropathy and has a very strong T cell suppressive activity. You have to be careful. You see more reactions with bortezomib than I saw with NINLARO. And carfilzomib is also an excellent drug, of course. It’s very active but has side effects, particularly in elderly patients. The NINLARO works very well in young and in elderly patients, and patients without high-risk cytogenetic factors.

Maria-Victoria Mateos, MD, PhD: Ixazomib is different to the other proteasome inhibitors. It’s a boronic type of proteasome inhibitor, and bortezomib is also a boronic type proteasome inhibitor. However, carfilzomib is a second-generation proteasome inhibitor. It’s an epoxyketone proteasome inhibitor. The mechanism of action is different, and although the 3 proteasome inhibitors target the proteasome, the exact mechanism of action is not exactly the same.

In terms of activity, I think that it’s not easy to compare the 3 proteasome inhibitors, mainly because they have not been compared in a phase III randomized trial so far. I would say that the proteasome inhibition is a key mechanism of action relevant for the treatment of all patients with multiple myeloma. What is important is that bortezomib was the first proteasome inhibitor used in the clinic. The second-generation proteasome inhibitors, carfilzomib and ixazomib, are effective in patients previously treated and even in patients who are refractory to the first-generation proteasome inhibitor. I would say that the 3 proteasome inhibitors we have now in our clinic are complementary—more than a strategy—alternatives. And I think that we can probably use the 3 proteasome inhibitors along the course of the disease of 1 specific myeloma patient.

Transcript Edited for Clarity