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ASCO 2012 Multiple Myeloma Update – Day Four: Immunotherapy For Myeloma
By: The Myeloma Beacon Staff; Published: June 4, 2012 @ 5:28 pm | Comments Disabled
Today is the fourth day of the American Society of Clinical Oncology (ASCO) 2012 annual meeting, and the meeting continued to be filled with interesting results from clinical trials in multiple myeloma patients.
The day included a session of oral presentations in the late morning that featured results from three clinical trials involving immunotherapy agents.
The three compounds, elotuzumab [1], siltuximab [2], and daratumumab [3], belong to the class of drugs called monoclonal antibodies. They work by identifying proteins on the surface of myeloma cells and signal for the immune system to destroy the cancer cells. All three drugs are administered via infusion, rather than as a tablet or capsule.
The results presented during the session can be considered good news for myeloma patients. Two of the three drugs showed promising results in terms of both efficacy and tolerability, and one of those drugs -- elotuzumab -- is already in late stage clinical trials.
Elotuzumab
Elotuzumab, which is being developed by Bristol-Myers Squibb (NYSE: BMY), is the monoclonal antibody that is furthest along in clinical development for multiple myeloma.
During the session this morning, Dr. Philippe Moreau from the University Hospital in Nantes, France, presented updated results from a Phase 2 study of elotuzumab in combination with Revlimid [4] (lenalidomide) and low-dose dexamethasone [5] (Decadron) in patients with relapsed and refractory multiple myeloma (abstract [6]).
The study included 73 patients. All patients were required to have had one to three previous lines of therapy. Patients previously treated with Revlimid could not participate in the trial.
Half of the patients received 10 mg/kg elotuzumab, while the other half received 20 mg/kg.
Preliminary results of the study presented at the American Society of Hematology’s annual meeting in December had already indicated that the lower dose seems to be more effective than the higher dose (see related Beacon [7] news).
The results Dr. Moreau presented today confirmed that trend.
Overall, 92 percent of patients in the 10 mg/kg group and 76 percent in the 20 mg/kg group responded to treatment. Among patients with just a single previous line of therapy, 91 percent had a partial response or better. Median progression-free survival across all the patients in the trial has not yet been reached after a median follow-up time of 17.2 months.
Serious side effects occurred in a limited number of patients and consisted primarily of low white blood cell counts and low platelet counts. There were, however, four cases of second cancer among the trial participants.
In his review of the three presentations given during this session, Dr. Andrzej Jakubowiak from the University of Chicago said that the elotuzumab combination demonstrates "very promising" efficacy and very good tolerability. Phase 3 trials of the drug in combination with Revlimid are already ongoing in both newly diagnosed and relapsed and refractory myeloma patients.
Siltuximab
Siltuximab is being developed by Janssen Biotech, a Johnson & Johnson company (NYSE: JNJ). The antibody blocks the activity of IL-6, a protein that facilitates myeloma cell growth and resistance to dexamethasone.
Dr. Robert Orlowski from the MD Anderson Cancer Center in Houston presented results from a Phase 2 study comparing siltuximab plus Velcade [8] (bortezomib) to Velcade alone (abstract [9]).
The study included 286 multiple myeloma patients with one to three previous lines of therapy. Patients were not permitted to have been previously treated with Velcade.
Results showed that more patients on siltuximab plus Velcade responded to treatment (55 percent) than patients on Velcade alone (47 percent).
The median progression-free survival time was longer for patients receiving siltuximab plus Velcade (8.1 months), compared to patients receiving Velcade alone (7.6 months).
However, the median overall survival time was longer for patients receiving Velcade alone (36.9 months) compared to those receiving siltuximab plus Velcade (30.8 months).
More patients receiving siltuximab plus Velcade experienced severe or life-threatening side effects (91 percent) than patients receiving Velcade alone (74 percent).
Although the results of this trial were not what he and his colleagues initially expected, Dr. Orlowski noted that other trials investigating siltuximab as a potential treatment for myeloma are still ongoing or planned.
Dr. Orlowski has made his presentation available [10] for download and viewing as a courtesy to The Beacon's readers.
Daratumumab
Daratumumab is being developed by the Danish pharmaceutical company Genmab. It is a monoclonal antibody that binds to the CD38 molecule, which is found on the surface of multiple myeloma cells. Daratumumab then signals for the immune system to kill the myeloma cells.
Dr Torben Plesner from Vejle Hospital in Vejle, Denmark, presented preliminary efficacy results from a Phase 1/2 study of daratumumab in relapsed and refractory myeloma patients (abstract [11]).
Twenty-nine patients included in the study received varying doses of daratumumab up to 16 mg/kg, along with occasional doses of dexamethasone.
To participate in the trial, patients had to have at least two previous lines of therapy, and most patients had considerably more than that. All patients previously received treatment with Velcade and either Revlimid or thalidomide.
Treatment with daratumumab achieved a partial response in 24 percent of the patients, a minimal response in 14 percent of the patients, and stable disease in another 24 percent of the trial participants.
According to the researchers, the drug’s side effects at these doses are manageable. Specifically, 14 percent of patients experienced serious side effects, including low red blood cell and platelet counts, abnormal liver function tests, spasms of the airways making breathing difficult, and an inflammatory syndrome.
Dr. Plesner said that additional studies with myeloma patients are planned that will look at continuous daratumumab therapy and also daratumumab in combination with Revlimid or Velcade plus dexamethasone.
For further details, see the slide deck [12] (PDF) for Dr. Plesner’s presentation, which he has made available as a courtesy to The Beacon’s readers.
In his discussion of the daratumumab results, Dr. Jakubowiak described the drug as "very active" with no significant toxicity issues. He also noted that the results may be even more promising than they seem at first glance. In Dr. Plesner's trial, the drug showed greater efficacy at its higher doses, and there seems to be scope to increase the dose beyond what has been tested in the trial so far.
Myeloma presentations from later today, Day 4, of the ASCO 2012 meeting also will be summarized in ASCO daily updates to be published later today or 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 [13] coverage.
Article printed from The Myeloma Beacon: https://myelomabeacon.org
URL to article: https://myelomabeacon.org/news/2012/06/04/asco-2012-multiple-myeloma-update-day-four-immunotherapy-for-myeloma/
URLs in this post:
[1] elotuzumab: https://myelomabeacon.org/tag/elotuzumab/
[2] siltuximab: https://myelomabeacon.org/tag/siltuximab
[3] daratumumab: https://myelomabeacon.org/tag/daratumumab
[4] Revlimid: https://myelomabeacon.org/resources/2008/10/15/Revlimid
[5] dexamethasone: https://myelomabeacon.org/resources/2008/10/15/dexamethasone/
[6] abstract: http://abstract.asco.org/AbstView_114_92546.html
[7] Beacon: https://myelomabeacon.org/news/2011/12/14/elotuzumab-combination-effective-for-relapsed-refractory-multiple-myeloma-ash-2011/
[8] Velcade: https://myelomabeacon.org/resources/2008/10/15/velcade/
[9] abstract: http://abstract.asco.org/AbstView_114_96732.html
[10] available: http://bit.ly/LuCJNM
[11] abstract: http://abstract.asco.org/AbstView_114_96350.html
[12] slide deck: http://bit.ly/M0Z4S5
[13] ASCO 2012: https://myelomabeacon.org/tag/asco-2012-meeting/
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