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.
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New treatments for multiple myeloma (MM) are changing the treatment landscape and that is set to continue over the next few years as several new products come to market.
This year we have seen the FDA approval of subcutaneous bortezomib (Velcade®) and carfilzomib (Kyprolis®). Approval for pomalidomide is anticipated soon.
Earlier this week at the 2012 Chemotherapy Foundation Symposium in New York, Sundar Jagannath, M.D., Professor of Medicine at Mt. Sinai School of Medicine presented on “New IMiD and Proteasome Inhibitors.”
Dr Jagannath told a large audience at the Symposium (also known as the Greenspan Meeting) that he hoped “pomalidomide will get accelerated approval and be in your hands by New Year”.
In his presentation, Jagannath discussed some of the new products in development. One that he mentioned in detail was MLN9708/ixazomib (Millennium), a new reversible, oral proteasome inhibitor currently in early clinical trials.
He noted that is not just being developed as a single agent in advanced disease, but is already being tested in combination with lenalidomide and dexamethasone therapy in earlier settings.
Companies with MM drugs in the pipeline will need to look closely as to how the treatment landscape may change in the next few years if new products such as ixazomib are approved and replace existing products such as bortezomib.
Although Dr Jagannath’s talk was very informative from a new product development perspective, I did wonder whether some of the community medical oncologists in the audience, who only see a few myeloma patients, might have benefitted from a more practice orientated perspective.
I sat next to a community oncologist from Florida, for example, who told me he found the MM treatment regimens difficult to understand for the few patients that he saw.
Dr Jagannath concluded his presentation with the thought that “rapid strides in genomics promises new drugs and personalized medicine in the near future.”
I look forward to hearing more about the latest research in Multiple Myeloma at the annual meeting of the American Society of Hematology (ASH 2012) in Atlanta next month.