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.
One of the enduring legacies from the development of imatinib (Gleevec®/Glivec®) for the treatment of chronic myeloid leukemia (CML) is the long-term survival data from the IRIS (International Randomized Interferon versus STI571) trial that enrolled 1106 patients between June 2000 and January 2001.
Hagop Kantarjian, M.D. Professor and Chair, Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston told the 2012 Chemotherapy Foundation Symposium (also known as the Greenspan Meeting in honor of the late Ezra Greenspan, M.D.) that:
the 10 year survival rate is 85% in patients treated with imatinib, and that this rises to 90% if you exclude deaths not related to CML.
No second-generation tyrosine kinase inhibitor (e.g. nilotinib, dasatinib, bosutinib) has yet to show a superior long-term survival benefit to imatinib. Dr Kantarjian noted that “whatever comes as a new treatment in the frontline therapy has to be able to beat that time, of a 10 year survival, if there is a big cost difference.”
The IRIS trial survival data for imatinib remains the gold standard by which other tyrosine kinase inhibitors will be judged.
In other words, notwithstanding the myriad of published CML data that shows second generation TKIs offer a deeper or more rapid molecular response, there’s still no data that shows you will actually live longer if you take any of them instead of imatinib.
That’s not to say there are no benefits to the newer second generation TKIs.
This morning the 8am session at the Chemotherapy Foundation Symposium (The Greenspan Meeting) in NYC featured a review of current developments in Prostate Cancer.
The informative 1.5 hour session covered a lot of ground with the presenters reviewing clinical data for:
- Radium-223 Chloride: a new option for CRPC (Oliver Sartor)
- Pomegranite extract for Rising PSA (Michael Carducci)
- XL184 in mCRPC (David Smith)
- Optimizing patient selection for sipuleucel-T (Simon Hall)
- Intermittent androgen suppression for prostate cancer (Laurence Klotz)
- Lenolidomide/docetaxel in CRPC (Daniel Petrylak)
The highlight, in my opinion, was Oliver Sartor’s excellent presentation on radium-223 chloride (Alpharadin) in which he cogently outlined its mechanism of action. He explained that radium-223:
- targets osteoblastic bone metastases by acting as a calcium mimic
- is a bone-seeking calcium mimetic that binds to hydroxyapatite
- has preferential uptake in areas of new bone formation
As mentioned previously on this blog, there are critical differences between an alpha emitter such as radium-223 and other bone-seeking radiopharmaceuticals that are beta emitters.
Sartor presented some excellent slides that showed how alpha emitters require much fewer DNA hits to kill cells, are short range and have a higher initial energy per particle. In other words they are very effective at short range within the bone microenvironment, something that Chris Parker from The Royal Marsden Hospital mentioned in his interview from ECCO/ESMO in Stockholm.
Sartor concluded his Chemotherapy Foundation Symposium presentation by reflecting on “where do we go from here” in prostate cancer? Some of his observations were:
- We are currently in a sequencing paradigm. Drug A then B then C
- We need to combine active agents to give the best results, that is our next challenge
- How are we going to afford it all?
Sartor succinctly highlighted where the rubber currently hits the road, and left the audience with plenty to reflect upon. I am sure we can expect further debate on sequencing and combination possibilities at medical and scientific meetings in 2012.