ASH 2012 Multiple Myeloma Update – Day Two: Early Afternoon Oral Session
Published: Dec 9, 2012 5:53 pm; Updated: Dec 16, 2012 7:45 pm


This year’s American Society of Hematology (ASH) annual meeting, which is being held in Atlanta, began yesterday and goes through Tuesday.
Today’s myeloma-related presentations began this afternoon with three sessions of oral presentations. Two of the sessions focused on results from clinical trials, most of which studied drugs that are still under development as potential treatments for multiple myeloma. The third session, which focused on the biology of myeloma, ran simultaneously with one of the sessions about clinical trial results.
This article will summarize the first oral session about multiple myeloma treatments, which took place from noon to 1:30 in the afternoon.
Although the session was relatively low-key -- as most medical conference sessions are -- the presentations during the session included results that are genuinely exciting.
There were results, for example, for three drugs (daratumumab, dinaciclib, and circularly permuted TRAIL) that are significantly different from any of the drugs currently approved to treat multiple myeloma. That in and of itself is significant, because new classes of drugs typically improve the treatment options available to patients.
Yet, even more importantly, the study results for these three drugs suggest they have real promise as future myeloma treatments.
Similarly, two of the studies that were presented involved combination treatments for heavily pretreated patients, and the response rates and survival rates for those combination regimens are noticeably higher than what has been seen in the past in this difficult-to-treat patient population.
Daratumumab
Dr Torben Plesner from Vejle Hospital in Vejle, Denmark, gave the first presentation during the session. He presented intermediate efficacy results from a Phase 1/2 study of daratumumab in relapsed and refractory myeloma patients (abstract; presentation slide deck (pdf) made available by Dr. Plesner as a courtesy to the Beacon’s readers).
Daratumumab is being developed by the Danish pharmaceutical company Genmab together with Janssen Biotech, a Johnson & Johnson (NYSE: JNJ) subsidiary. The drug is a monoclonal antibody that binds to the CD38 molecule, which is found on the surface of multiple myeloma and other blood cancer cells. Once it is bound to the CD38 molecule on cancer cells, daratumumab signals for the immune system to kill the cells.
The study that Dr. Plesner presented included 32 heavily pretreated myeloma patients who had received a median of 6.3 prior treatment regimens.
During the study, participants received escalating doses of daratumumab ranging from 0.005 mg/kg to 24 mg/kg.
Of the 32 patients included in the study, 47 percent showed a reduction in the amount of monoclonal (M) protein in the blood or urine, which corresponded to the following response rates: 13 percent of patients achieved a partial response, 19 percent a minor response, and 16 percent stable disease.
The maximum tolerated dose has not been reached yet.
According to the researchers, daratumumab showed a favorable safety profile.
Pomalidomide Plus Kyprolis And Dexamethasone
The next presentation was given by Dr. Jatin Shah from the M.D. Anderson Cancer Center in Houston. Dr. Shah presented results from a Phase 1/2 study of pomalidomide in combination with Kyprolis (carfilzomib) and dexamethasone (Decadron) (abstract; presentation slide deck (pdf) made available by Dr. Shah as a courtesy to the Beacon’s readers).
Pomalidomide is an immunomodulatory agent, meaning that it works by inducing a patient’s immune system to attack and destroy myeloma cells. It belongs to the same class of drugs as thalidomide (Thalomid) and Revlimid (lenalidomide).
Pomalidomide is being developed by Celgene Corporation (NASDAQ: CELG), the same company that markets Revlimid and thalidomide in the United States and internationally.
The study included 32 relapsed and refractory myeloma patients with a median age of 64 years. They were a median of five years from diagnosis and had been treated with a median of six prior lines of therapy.
Of the 30 patient evaluable for response, half of the patients responded, with 13 percent achieving a very good partial response and 37 percent achieving a partial response.
The median progression-free survival was 7.4 months, and at one year, 90 percent were alive.
The most common side effects were low white blood cell counts (84 percent), low red blood cell counts (63 percent), low platelet counts (57 percent), and fatigue (56 percent).
Revlimid, Thalidomide, And Dexamethasone
Dr. Shah also gave the third talk of the session. During this presentation, Dr. Shah discussed results from a Phase 1/2 study of Revlimid in combination with thalidomide and dexamethasone (abstract; presentation slide deck (pdf) made available by Dr. Shah as a courtesy to the Beacon’s readers).
Revlimid and thalidomide both belong to the same class of drugs known as immunomodulatory agents. Typically drugs from different classes are administered together to treat myeloma. Two immunomodulatory agents have never been studied in combination before. However, preclinical studies have shown that thalidomide can reverse resistance to Revlimid, indicating that it may be beneficial to administer the two drugs together for patients who have relapsed or stopped responding to treatment.
Dr. Shah reported results from 64 myeloma patients who had been treated with a median of four prior lines of therapy. The median patient age was 65 years.
Among the 61 patients evaluated for response, 51 percent responded. Specifically, 13 percent achieved a complete or near complete response, 7 percent achieved a very good partial response, and 31 percent achieved a partial response.
Among the 41 patients evaluated who previously did not respond to Revlimid, 34 percent responded to the combination therapy, with 5 percent achieving a complete or near complete response, 2 percent achieving a very good partial response, and 27 percent achieving a partial response.
Median progression-free survival was 8.0 months, and median overall survival was 29 months.
The most common side effects were fatigue (72 percent), shortness of breath (56 percent), constipation (55 percent), diarrhea (55 percent), low platelet counts (50 percent), and low red blood cell counts (47 percent).
Dinaciclib
Dr. Shaji Kumar from the Mayo Clinic in Rochester, Minnesota, then discussed results of a Phase 1/2 study of dinaciclib (abstract; presentation slide deck (pdf) made available by Dr. Kumar as a courtesy to the Beacon’s readers).
Dinaciclib is being developed by Merck (NYSE: MRK). It is a small molecule that inhibits enzymes called cyclin-dependent kinases, which regulate the cell cycle and are often overactive in cancer cells. Inhibition of these enzymes and interruption of the cell cycle causes the cell to die.
The results are from 27 patients with relapsed multiple myeloma who had received a median of four previous lines of therapy.
Overall, 15 percent responded, with 8 percent achieving a very good partial response and 7 percent achieving a partial response.
After a median follow-up time of 14.5 months, the progression-free survival rate was 22 percent and the overall survival rate was 44 percent.
The most common side effects were diarrhea (74 percent of patients), fatigue (52 percent), low platelet counts (48 percent), and nausea (44 percent).
Researchers are planning an upcoming Phase 1 clinical trial that will study dinaciclib in combination with Velcade (bortezomib) and dexamethasone.
Pomalidomide Plus Clarithromycin And Dexamethasone
The next presentation was by Dr. Tomer Mark from the Weill Cornell Medical School in New York City. He spoke about results from a Phase 2 study of pomalidomide in combination with clarithromycin (Biaxin) and dexamethasone, a combination sometimes referred to as ClaPD (abstract; presentation slide deck (pdf) made available by Dr. Mark as a courtesy to the Beacon’s readers).
Clarithromycin is an antibiotic used to treat bacterial infections, and it has been shown to improve the anti-myeloma activity of Revlimid and dexamethasone.
The study included 100 myeloma patients who had been treated with a median of five prior lines of therapy. The median age of the patients was 63 years.
Of the 98 patients evaluable for response, 57 percent of patients responded, with 6 percent achieving a stringent complete response, 17 percent a very good partial response, and 34 percent a partial response.
Median progression-free survival was 8.6 months, and median overall survival has not yet been reached after a mean follow-up time of 9.6 months.
The most common severe side effects were low white blood cell counts (47 percent), low platelet counts (27 percent), and low red blood cell counts (25 percent).
Circularly Permuted TRAIL
The session concluded with a talk by Dr. Wenming Chen from the Chaoyang Hospital of Capital Medical University in Beijing. Dr. Chen presented results of a Phase 2 study of circularly permuted TRAIL (abstract).
Circularly Permuted TRAIL (CPT) is being developed by Beijing Sunbio Biotech as a treatment for multiple myeloma and other blood cancers. It activates receptors in the body called TRAIL that cause cells to die. Preclinical studies have shown that CPT kills cancers cells but not most healthy cells.
The study included 27 people with relapsed or refractory multiple myeloma who had been treated with a median of three prior lines of therapy. The median patient age was 59 years.
Overall, 33 percent of the study participants responded to CPT treatment, including 4 percent who achieved a near complete response and 30 percent who achieved a partial response.
The most common side effects were fever (48 percent), elevated liver enzymes (41 percent), and low white blood cell counts (26 percent).
Myeloma presentations from the rest of Day 2 as well as Day 3 and Day 4 of the ASH 2012 meeting also will be summarized in ASH daily updates to be published at The Beacon the next few days. 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 ASH meeting, see The Beacon’s full ASH 2012 coverage.
Related Articles:
- Nelfinavir-Velcade Combination Very Active In Advanced, Velcade-Resistant Multiple Myeloma
- Nelfinavir Shows Only Limited Success In Overcoming Revlimid Resistance In Multiple Myeloma Patients
- Adding Clarithromycin To Velcade-Based Myeloma Treatment Regimen Fails To Increase Efficacy While Markedly Increasing Side Effects
- Revlimid, Velcade, and Dexamethasone, Followed By Stem Cell Transplantation, Yields Deep Responses And Considerable Overall Survival In Newly Diagnosed Multiple Myeloma
- ASCO 2018 Update – Expert Perspectives On The Key Multiple Myeloma-Related Oral Presentations
This article has been updated with links to presentation slide decks provided by Dr. Plesner (daratumumab) and Dr. Kumar (dinaciclib).
Thanks MB for the slides!
Regarding dinaciclib...these results don't look promising.
66% had disease progression
55.6% were dead within 21 months
and the drug is most active in neuronal cells vs. MM cells?
hmmmmmmm
Also thanks to Dr. Kumar and Plesner for the slides!
Daratumumab data looks promising.
Did Dr. Plesner say what the incidence of CD38 expression was for MM patients? Do all MM patients express CD 38 on their MM cells? Also did he indicate whether all MM cells express CD38 on their surface or is there only a certain percentage of myeloma cells expressing the CD38 relative to other blood cancers?
Links to PDF files with both of Dr. Shah's presentations during this session have been added to this article.
This article has been updated with a link to the clarithromycin-pomalidomide-dex slide deck that Dr. Mark discussed during his presentation.
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