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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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