Major Myeloma Themes at ASCO 2014
The ASCO conference is the largest oncology conference in the world, where over 25,000 experts gather to discuss recent announcements in cancer research. For all myeloma-related announcements from the conference, click here.
Some major themes in myeloma included:
Success with an HDAC Inhibitor - Panobinostat
Panobinostat is an histone deacetalyse inhibitor (HDAC) that was recently in trial. The study showed that panobinostat in combination to bortezomib and dexathasone extended progression-free survival in relapsed myeloma by four months compared to bortezomib and dex alone. The PANORAMA 1 Study results are described by Dr. Paul Richardson. Because of this success Novartis announced that they will be applying for priority review of drug status. (What does an HDAC inhibitor do?)
A Study for High Risk Myeloma Patients Using a Monoclonal Antibody
A new study was announced specifically for high risk myeloma patients with the 14;20 or 14;16 translocations or 17p deletion. This is the first national study led by Dr. Saad Usmani, MD to target the high risk patient population and will compare lenalidomide, bortezomib and dex (RVD) with or without the monoclonal antibody elotuzumab. Elotuzumab is a monoclonal antibody that targets the CS1 protein and has shown to be effective in combination with other myeloma therapies but only marginally alone. Dr. Paul Richardson, MD of the Dana Farber Cancer Institute describes elotuzumab in more detail:
Now, one of the leaders is a molecule called elotuzumab which targets a marker on the myeloma cell originally called CS1 but now called SLAMF7. And the important point is that this marker seems to be fairly unique to myeloma, although it is expressed on some other tissues but to a much less significant degree.
Elotuzumab on its own didn’t seem to do too much in advanced myeloma. It was relatively safe but best generated stable disease in the clinical trials that we did it. However, when you combine elotuzumab with drugs like lenalidomide, it’s almost like you generate a super charger effect where basically the two drugs synergize and not only seem to modulate aspects of the immune system but also seem to have a direct, what we call apoptotic effect on cell signaling. So it’s not just immunologically, it’s immunological effects plus others that drive it.
So the combination of elotuzumab with lenalidomide, the combination of elotuzumab even with bortezomib, all of these approaches have shown great promise, and in particular elotuzumab plus lenalidomide I think is going to go forward as an approval finding platform, hopefully, in a not too distant future, within the next year or so. So elotuzumab has been a big one.
Both monoclonal antibodies that target CD38 protein found on most myeloma cells (daratumumab and SAR650984) were discussed and show significant promise. Results from a daratumumab study by the Netherlands group for relapsed/refractory patients showed single agent activity and another study showed results when combined with lenalidomide. Daratumumab will continue in a variety of advanced phase studies based on its exciting results. Dr. Robert Orlowski of MD Anderson described one such study in a
The phase two, by the way, in the current cohort that’s open, it has about 60 slots and you may know that daratumumab has a designation from the Food and Drug Administration as a breakthrough therapy because of the very encouraging data. In the old days, that used to be fast track status. That means that the FDA is very excited about the data and they will review it very quickly when available for a possible approval.
The randomized study is much larger. I don’t remember the exact number, but it’s somewhere in the 600 to 700 patient range, I believe. So the good news about that is that it will be open for quite a while and hopefully give lots of people the opportunity to participate.
Dr. Thomas Martin of UCSF presented the SAR650984 results of a Phase I study also for relapsed/refractory patients and another Phase 1b study using SAR combined with lenalidomide and dexamethasone.
Continuous Maintenance Therapy?
This paper may make myeloma patients weary. Dr. Antonio Palumbo presented a paper showing that for newly diagnosed myeloma patients, continuous maintenance therapy after initial therapy is better than no maintenance therapy after initial therapy. The study compared two approaches: The first approach compared lenalidomide-based induction, consolidation, followed by maintenance vs. lenalidomide-based induction, consolidation, no maintenance.
The second approach compared bortezomib-based induction followed by maintenance vs. bortezomib-based induction, no maintenance.
In both groups. progression free survival was better when continuous maintenance therapy was used, but the study also showed that the lenalidomide group had longer progression free survival for each of the data points. It would be interesting to see continuous maintenance therapy compared to 1-2 years of maintenance therapy as is the norm in myeloma care today.
Metformin to Prevent Myeloma Progression?
A study by the Washington University School of Medicine showed the diabetic drug, metformin, when used for a prolonged period of time, was protective of MGUS progressing to myeloma in a percentage of patients. Over 2,000 MGUS patients with diabetes were studied retrospectively and showed that metformin use over 5.4 years made a large difference in the percentage that progressed to active myeloma and those that did not.
A New Drug called TH-302
A study by Dr. Jacob Laubach, Dana Farber Cancer Institute and several other facilities shared safety study results of TH-302, a hypoxia-targeted drug with dexamethasone. Hypoxia exists where tissues are not oxygenated properly, usually because of an insufficient concentration of oxygen in the blood. Hypoxia occurs in the bone marrow environment for myeloma patients, so it may prove to be an attractive target. TH-302 is selectively activated when hypoxia exists and kills myeloma cells in vitro and in vivo (mouse models). This study was the first in relapsed/refractory patients and a safety dosage with dex was determined.
Where Else Can Myeloma Patients Find ASCO 2014 Reviews?
Follow #ASCO14 on Twitter
Highlights of ASCO 2014 - MyelomaCinderella