ASCO 2012 Multiple Myeloma Update – Day Four: Poster Presentations On New Myeloma Treatments

This year’s American Society of Clinical Oncology (ASCO) annual meeting, which is being held in Chicago, began on Friday and goes through tomorrow. However, today is the last day with any myeloma-related sessions.
Several myeloma-related oral presentations were given this morning and were summarized in an update published earlier today (see related Beacon news).
This afternoon featured a poster session in which important new research findings were summarized on posters throughout a large conference hall.
The studies presented this afternoon were on a wide variety of myeloma-related topics ranging from new treatments being developed for myeloma, to currently used regimens, to secondary cancers, to precursor myeloma diseases, and much more.
This update covers some of the myeloma-related studies presented during the poster session. In particular, this article covers posters about new treatments that are being developed for myeloma. Some of the posters included preliminary results from ongoing clinical trials. Others described the design of ongoing clinical trials for which results are not yet available.
Additional updates will summarize posters from this afternoon that were about other myeloma-related topics.
Carfilzomib
The session included posters about three different carfilzomib (Kyprolis) studies, one of which -- described a bit further below -- studied the combination of carfilzomib and panobinostat (Farydak).
Carfilzomib is being developed by Onyx Pharmaceuticals (NASDAQ: ONXX). It works similarly to Velcade (bortezomib) and is currently being reviewed by the U.S. Food and Drug Administration for potential approval as a new myeloma treatment.
One poster highlighted results from a Phase 1/2 study of the safety and efficacy of carfilzomib as a replacement therapy for Velcade in patients who progressed while taking Velcade-containing regimens (abstract). Early results of the study suggest that carfilzomib is an effective and tolerable replacement for Velcade in these patients.
The study included 27 patients who had received a median of six previous lines of therapy. Of the 27 patients, 22 of whom were evaluated for response. The overall response rate was 51 percent, with 23 percent of patients achieving a complete response, 5 percent a very good partial response, and 23 percent a partial response.
The median progression-free survival time was 9.8 months.
The most common severe side effects were low platelet and lymphocyte counts as well as fever, pneumonia, and sepsis.
Another carfilzomib poster summarized results of an analysis of the safety of carfilzomib in relapsed and refractory myeloma patients. In the analysis, researchers assessed the rate of various blood-related side effects in 526 myeloma patients treated with single-agent carfilzomib across four different Phase 2 studies (abstract).
According to the study investigators, 70 percent of patients treated with carfilzomib experienced blood-related side effects. However, severe to life-threatening blood-related side effects were both infrequent and lasted for short periods of time. These included low platelet, lymphocyte, neutrophil, and red blood cell counts.
Based on their results, the researchers concluded that the safety profile of carfilzomib was similar to or better than that of currently approved myeloma therapies.
Carfilzomib Plus Panobinostat
The final carfilzomib-related poster described an ongoing Phase 1/2 clinical trial evaluating the safety and efficacy of the combination of carfilzomib plus panobinostat for the treatment of relapsed and refractory multiple myeloma (abstract). Results are not yet available for this trial.
Panobinostat is an oral drug that is being developed by the pharmaceutical company Novartis (NYSE: NVS) for a variety of different cancers. It belongs to a class of drugs called histone deacetylase (HDAC) inhibitors, which work by increasing the production of proteins that slow cell division and cause cell death.
The study plans to enroll up to 52 relapsed or refractory myeloma patients.
The Phase 1 portion of the study will include approximately 24 patients and will determine the maximum tolerated doses of carfilzomib and panobinostat when administered together.
In the Phase 2 portion of the study, approximately 25 patients will receive treatment with the optimal doses of the carfilzomib-panobinostat combination. Researchers will then evaluate the overall response rate, time to progression, progression-free survival, and overall survival of patients treated with this regimen as well as the safety of the regimen.
Elotuzumab
The session also included four different posters about elotuzumab studies.
Elotuzumab is a monoclonal antibody being developed by Bristol-Myers Squibb (NYSE: BMY). It works by identifying proteins on the surface of myeloma cells and signalling for the immune system to destroy the cancer cells.
Three posters described the designs of ongoing clinical trials investigating elotuzumab-containing regimens. Results are not yet available for these trials.
Two of the studies are Phase 3 clinical trials investigating the combination of elotuzumab, Revlimid (lenalidomide), and dexamethasone (Decadron) compared to Revlimid plus dexamethasone alone.
One of these trials plans to test the combination in 750 newly diagnosed myeloma patients who are ineligible for stem cell transplantation (abstract). The other plans to test the combination in 640 relapsed and refractory myeloma patients (abstract).
Another ongoing study is a Phase 2 clinical trial investigating the combination of elotuzumab, Velcade, and dexamethasone compared to Velcade plus dexamethasone alone (abstract). The trial plans to test the combination in 150 relapsed and refractory myeloma patients.
In each of these trials, patients will be evaluated for response. Progression-free survival and overall survival will also be tracked.
Another poster presented a laboratory study in which researchers investigated whether the combination of elotuzumab plus Revlimid demonstrates greater anti-myeloma activity compared to elotuzumab or Revlimid alone (abstract).
The researchers found that when myeloma cells and blood cells were incubated with elotuzumab or Revlimid alone, some of the myeloma cells died. However, significantly more myeloma cells were killed when treated with the combination of elotuzumab and Revlimid. The researchers also showed that elotuzumab activated certain immune cells known as natural killer cells, which kill myeloma cells.
SNS01-T
Another poster from the session described the design of an ongoing Phase 1/2 trial investigating the safety and tolerability of SNS01-T in relapsed and refractory multiple myeloma patients (abstract). Results are not yet available for this trial (see update below).
SNS01-T is being developed by the pharmaceutical company Senesco (NYSEAMEX: SNT). It selectively causes cells to die by targeting a protein called eIF5A, which is believed to be an important regulator of cell growth and cell death.
The trial plans to enroll 15 patients who are not eligible for any standard treatment options. They will be divided into several groups, each of which will receive a higher dose of SNS01-T.
Participants will be evaluated for response, and progression-free and overall survival will also be tracked.
Update (June 6, 2012; 11:00 am) - In a press release issued on Monday, Senesco released initial results from the trial that were not included in the poster presented at ASCO. The company reported that five patients have been enrolled in the study so far. Additionally one has completed treatment and has achieved stable disease. However, two patients discontinued therapy due to disease progression. No dose-limiting side effects have been reported.
Myeloma Vaccine
The search for vaccines to treat multiple myeloma and other cancers has been under way for several years. Another poster from this afternoon’s session described the design of an ongoing Phase 1 clinical trial investigating a vaccine for the treatment of myeloma patients undergoing stem cell transplantation (abstract). Results are not yet available for this trial.
The vaccine, which is being developed by GlaxoSmithKline (NYSE: GSK), targets the protein MAGE-A3, which is present on the surface of myeloma and other cancer cells, but not normal cells. The vaccine trains immune cells to attack cells with MAGE-A3 on their surface. The vaccine is in Phase 3 trials for lung cancer and melanoma. However, this is the first time the vaccine is being tested for myeloma or in patients undergoing stem cell transplantation.
The trial plans to enroll 16 patients who have been diagnosed with multiple myeloma within the last year and achieved at least a very good partial response to their induction therapy.
Patients will be vaccinated six weeks before their stem cell transplant. Three weeks after vaccination, lymphocytes (a type of immune cell that have hopefully been trained by the vaccine to attack myeloma cells) will be collected. These will be re-infused three days after stem cell transplantation. Patients will be vaccinated seven more times within the nine months following their transplant.
Additional myeloma-related posters from today, Day 4 of the ASCO 2012 meeting, also will be summarized in ASCO daily updates to be published tomorrow. Additional coverage of key research results from the meeting will continue throughout the rest of the week in individual, topic-specific news articles.
For all Beacon articles related to this year’s ASCO meeting, see The Beacon’s full ASCO 2012 coverage.
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- U.S. FDA Okays First Clinical Trial Of An Allogeneic CAR T-Cell Therapy For Multiple Myeloma
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Thanks for the great article , Julie. On the topic of the MAGE-A3 vaccine test, I see that the vaccination, six weeks before transplant, but after induction chemo I assume, would save the lymphocytes for re-infusion after the melphalan had destroyed the patient's bone marrow (SCT). Did they say in the full paper whether the leukaphoresis (collection of the lymphocytes) would occur before the aphoresis collection of the patient's own stem cells (assuming this is an auto type collection)? I ask this because strong chemo is also used before stem cell collection, and it possibly could damage the lymphocytes.
Hi Nancy,
Thanks for the follow-up questions. As you suspected, participants will receive induction therapy followed by vaccination, lymphocyte collection, then stem cell collection, high-dose chemotherapy with melphalan, and finally stem cell transplantation and re-infusion of the lymphocytes.
Hi Julie,
Did the authors mention the possibility of purging the lymphocytes of CD20+ B cells which are potentially MM Stem cells (according to Bill Matsui-Hopkins model) and not desirabable to be reinfused after transplant? Most of the benefit of the vaccine would probably come from the killer T cells anyway.
If we are going to make real progress and cure myeloma we need to consider all the science for the benefit of the patients!
Hi Dan,
The authors do not mention purging the lymphocytes, or the stem cells for that matter.
Dr. Adam Cohen, one of the Beacon's Medical Advisors, is the first author on the poster, so I will follow up with him to see if he can provide any further detail on the methods he and his colleagues will be using.
I appreciate this and the fine work of the Beacon Team Julie. Thanks
Hi all,
We are not doing any purging of the peripheral blood lymphocytes or stem cells in this study. Several studies in the 90's examined purging stem cell products of myeloma cells, without clinical benefit seen. The Hopkins group (and others) have tried to eliminate the putative CD20+ myeloma stem cell (which still remains a controversial concept) using rituximab post-SCT, again without clinical benefit seen. While our primary goal with the vaccination and initial leukopheresis is to activate and transfer "killer T cells", as you suggest, there are many vaccines where the primary protective effect is mediated by antibodies, which requires activation and expansion of CD20+ B cells. So there may be a real downside with regard to immunity by taking these cells out. Since we don't know yet which immune cells will be most important for response to the vaccine and for controlling the myeloma, we've opted not to manipulate the cell products in this study.
Hope this is helpful.
Best regards,
Adam Cohen
Thanks for the feedback Adam.
It seems you are involved in this exciting project. I didn't mean to criticize, just suggesting next steps to improve upon it. I am unique as a 25 year survivor with systemic AL-amyloidosis diagnosed in 1987 with 25 year remission without ASCT just interferon maintanance after two "experimental" therapies for those day (VAD then the Sloan Kettering M2 protocol- I think).
Diagnosed and followed Barlogie from MD Anderson to UAMS now getting treatment in collaboration with Stewart (Mayo-AZ) and Barlogie- a testament to pick the brightest minds your can find for your care. A concept I urge for all MM patients.
I am also a PhD tumor immunologist and cancer cell biologist with an interest in cancer stem cells. It doesn't surprise me that killing cancer stem cells takes more than rituximab because there are more survival signals than death signals both in the MM stem cells and the supportive "niche cells" that keep the cancer alive for future relapse.
All of the excellent discoveries made with the MM drugs are fantastic and definately leading to longer survival but once the patient is in remission (by whatever method we use) we need to go after the true source of the disease. I tell my students it's like trying to put out a fire, if you beat down the flames (MM plasma cells) without destroying the embers (MM Stem cells) it is only a matter of time before the fire returns.
I'd love to see an collaborative initiative in myeloma community (scientists, clinicians and even Pharma) perhaps under MMRF to develop anti-MM stem cell-targeted therapy.
It could be our best hope for a real cure and as I alluded to earlier the basic science science is beginning to be developed.
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