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ASCO 2013 Multiple Myeloma Update – Day Three: Poster Presentations

By: Virginia Li; Published: June 3, 2013 @ 9:27 pm | Comments Disabled

This year’s American Society of Clinical Oncology (ASCO) annual meeting, which is being held in Chicago, began on Friday and goes through Tuesday.

Sunday started with a poster session in which important new research findings were summarized on posters displayed throughout a large conference hall.

The studies presented during the session were on a wide variety of myeloma-related topics, including new treatments being developed for myeloma, currently used regimens, smoldering multiple myeloma, and findings on initial therapy.

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.

This update covers many of the myeloma-related studies presented during Sunday’s poster session.

TH-302

The session included a poster summarizing initial results from a Phase 1 study of TH-302 [1] plus dexa­metha­sone [2] (Decadron) in heavily pretreated myeloma patients (abstract [3]poster [4] [pdf] courtesy of Dr. Irene Gho­bri­al).

TH-302 is being developed by Threshold Pharmaceuticals (NASDAQ: THLD) and the German pharma­ceut­i­cal company Merck KGaA. TH-302 is a drug that is activated under low oxygen level conditions, which are common in tumors and the bone marrow of people with blood cancers. It is currently also being investigated in a range of solid tumors.

The study included 13 patients with a median age of 59 years who had received a median of six prior lines of therapy.

They were treated with one of three different doses of TH-302 plus dexamethasone.

Of the 12 patients evaluated for response, 17 percent achieved a partial response, 17 percent reached a minimal response, and 67 percent had stable disease.

The lower doses tested appear safe, but the highest dose was associated with severe side effects.

The authors point out that Velcade will be added to the combination for Phase 2 of the study.

Kyprolis

The session included two posters about Kyprolis [5] (carfilzomib), which was approved by the U.S. Food and Drug Administration (FDA) for the treatment of relapsed and refractory multiple myeloma last year.

The first poster summarized the findings of a Phase 1/2 study that investigated the safety and efficacy of Kyprolis when substituted for Velcade [6] (bortezomib) in Velcade-based regimens on which patients had progressed (abstract [7]; poster [8] [pdf] courtesy of Dr. James Berenson).

The study included 37 patients who had received a median of five prior therapies, including two Velcade-based combinations.

The results show that 43 percent of patients responded when Velcade was replaced with Kyprolis, with 8 percent achieving a complete response, 16 percent a very good partial response, and 19 percent a partial response.

The median time to progression was 9.9 months, and the median overall survival was 15.8 months.

The most common severe side effects included low lymphocyte levels (35 percent), low platelet counts (24 percent), low white blood cell counts (11 percent), and low red blood cell counts (3 percent).

The second Kyprolis-related poster described results of a retrospective analysis of heart-related compli­ca­tions in heavily pretreated myeloma patients who received treatment with Kyprolis.  The patients were given Kyprolis on a compassionate use basis at the University of Arkansas for Medical Sciences starting in 2009 (abstract [9]; poster [10] [pdf] courtesy of Dr. Saad Usmani).

The analysis included data from 143 patients with a median age of 61 years.  They had received a median of seven prior therapies; 92 percent had received a stem cell transplant, and 74 percent had received two or more transplants.

During the first 28-day cycle of treatment, patients received Kyprolis with dexamethasone, and the Kyprolis dosing was comparable to the current FDA-approved dosing regimen.

During the second and later cycles, Kyprolis's dose could be increased, and other anti-myeloma therapies could be added to the treatment regimen.

The results show that 19 percent of patients experienced a serious heart-related complication, 78 percent of whom had preexisting risk factors for heart-related complications. Nine percent of patients required hospitalization.

The researchers point out that the reasons for these heart-related complications could not be definitively determined because of the retrospective nature of the analysis, but suggest using Kyprolis with caution in patients with a history of serious cardiac disease.

Pomalyst

The session also included several posters about Pomalyst [11] (pomalidomide), which was approved earlier this year by the FDA for the treatment of relapsed and refractory myeloma.

One poster summarized the results of a Phase 1 study of Pomalyst in combination with Velcade and low-dose dexamethasone in relapsed and refractory multiple myeloma patients (abstract [12]; poster [13] [PDF] courtesy of Dr. Paul Richardson).

The study included 22 patients with a median age of 57 years who had received a median of two prior lines of therapies.

Among the 20 patients evaluated for response, the overall response rate was 75 percent.  Specifically, 5 percent achieved a complete response, 25 percent a very good partial response, and 45 percent a partial response.

The most common severe side effects were low white blood cell counts (32 percent) and low platelet counts (21 percent).

The second Pomalyst poster showed the results of a Phase 1/2 study of Pomalyst in combination with Doxil [14] (doxorubicin liposomal) and dexamethasone in relapsed and refractory multiple myeloma patients (abstract; [15] poster [16] [pdf] courtesy of Dr. James Hilger).

The study included 27 patients with a median age of 69 years who had received a median of five prior therapies.

Overall, 33 percent achieved a partial response. In addition, 4 percent achieved a minimal response and 26 percent reached stable disease.

The most common severe side effects were low white blood cell counts, including low leukocyte counts (41 percent), low neutrophil counts (37 percent), and low lymphocyte counts (30 percent).

Since more than half of the patients initially enrolled in the study experienced low white blood cell counts, the Pomalyst dose will be lowered from 4 mg to 3 mg for any additional patients enrolled in the study.

Another poster included initial results of a Phase 1 study investigating the efficacy and safety of Pomalyst plus low-dose dexamethasone in relapsed and refractory multiple myeloma patients with kidney impairment (abstract [17]).

The study included 11 relapsed and refractory myeloma patients, eight with normal kidney function and three with impaired kidney function that did not require dialysis.  Additional patients, including those requiring dialysis, are being recruited.

The median age of the participants so far is 66 years, and they had received a median of four prior lines of therapy.

Patients received 2 mg or 4 mg of Pomalyst, depending on their kidney function.

Among the 11 patients evaluated for response, the overall response rate was 27 percent, which is con­sis­tent with results from other studies of this combination.

The most common severe side effects were low white blood cell counts (50 percent for those with normal kidney function versus 33 percent for those with impaired kidney function), infections (25 percent versus 66 percent), and anemia (25 percent versus 33 percent).

No patients with kidney impairment required dose reductions or discontinued treatment due to side effects.  Additionally, the length of time on treatment was similar for both groups of patients (4.1 months for patients with normal kidney function and 3.9 months for those with impaired kidney function).

Rapidity Of Response To Initial Therapy

Another poster summarized the results of a retrospective analysis that investigated the implications of rapidity of response to initial therapy (abstract [18]; poster [19] [pdf] courtesy of Dr. Shaji Kumar).

The analysis was based on data from 454 newly diagnosed myeloma patients who underwent initial therapy between January 2000 and December 2011 at the Mayo Clinic in Rochester, Minnesota. The median age at diagnosis was 66 years.

The researchers found that overall survival times were shortest for patients who had very shallow responses (3.3 years) or very deep responses (5.1 years) after the first cycle of treatment, compared to the remaining patients (about 7.5 years).

Based on their results, the researchers believe that patients with shallow responses and well as those with very deep responses during the first treatment cycle should be considered as having high-risk disease.

They recommend additional studies to determine whether a change in treatment regimen would benefit patients who do not respond to therapy quickly.

SL-401

Another poster summarized the results of a preclinical study of the investigational drug SL-401 [20], which is being developed by Stemline Therapeutics (NASDAQ: STML) in cooperation with the Dana-Farber Cancer Institute in Boston (abstract [21]).

SL-401 works by targeting the interleukin-3 receptor found on tumor-promoting plasma­cytoid dendritic cells. Plasma­cytoid dendritic cells are a form of immune cells.

The results showed that SL-401 inhibited growth of myeloma cells by killing the tumor-promoting plasma­cytoid dendritic cells that are abundant in the bone marrow of myeloma patients.

Smoldering Multiple Myeloma

Another poster showed the results of a systematic review that investigated early versus late treatment of smoldering multiple myeloma (abstract [18]).

The review was based on seven studies that included 869 patients in total.  The treatments investigated in the studies were not all anti-myeloma therapies.  Instead, in almost half the studies, the treatments investigated were bisphosphonate therapies.

The results show that the risk of disease progression was lower in patients receiving early therapy com­pared to patients who did not.

The results also show that the use of combination therapy compared to single-agent therapy decreased the risk of progression.

However, the researchers did not observe any differences in overall survival between patients who received early treatment versus those who did not.

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Myeloma presentations from Day 4 will also be summarized in Beacon ASCO daily updates to be published in the upcoming days.  Additional coverage of key research results from the meeting will continue after the meeting is over with individual, topic-specific news articles.  For all Beacon articles related to this year’s ASCO meeting, see The Beacon’s full ASCO 2013 [22] coverage.

Note: Electronic copies of conference presentations and posters made available to the Beacon's readers are for personal use only. Further transmission or publication of the files is not permitted, although hyperlinks to the files are permitted with attribution to the author and to The Beacon (for example, "courtesy of Dr. Jane Doe and The Myeloma Beacon.")


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URL to article: http://www.myelomabeacon.com/news/2013/06/03/asco-2013-multiple-myeloma-update-day-three-poster-presentations/

URLs in this post:

[1] TH-302: http://www.myelomabeacon.com/tag/th-302/

[2] dexa­metha­sone: http://www.myelomabeacon.com/resources/2008/10/15/dexamethasone/

[3] abstract: http://meetinglibrary.asco.org/content/117529-132

[4] poster: http://www.myelomabeacon.com/docs/asco2013/Ghobrial-TH-302.pdf

[5] Kyprolis: http://www.myelomabeacon.com/tag/kyprolis/

[6] Velcade: http://www.myelomabeacon.com/resources/2008/10/15/velcade/

[7] abstract: http://meetinglibrary.asco.org/content/115893-132

[8] poster: http://www.myelomabeacon.com/docs/asco2013/Berenson-KyprolisVelcadeReplacement.pdf

[9] abstract: http://meetinglibrary.asco.org/content/114116-132

[10] poster: http://www.myelomabeacon.com/docs/asco2013/Atrash-KyprolisCardiovascularEvents.pdf

[11] Pomalyst: http://www.myelomabeacon.com/tag/pomalyst

[12] abstract: http://meetinglibrary.asco.org/content/111852-132

[13] poster: http://www.myelomabeacon.com/docs/asco2013/Richardson-PomVelDex.pdf

[14] Doxil: http://www.myelomabeacon.com/resources/2008/10/15/doxil/

[15] abstract;: http://meetinglibrary.asco.org/content/115804-132

[16] poster: http://www.myelomabeacon.com/docs/asco2013/Hilger-PomalystDoxilDex.pdf

[17] abstract: http://meetinglibrary.asco.org/content/111865-132

[18] abstract: http://meetinglibrary.asco.org/content/114097-132

[19] poster: http://www.myelomabeacon.com/docs/asco2013/Ghimire-RapidityOfResponse.pdf

[20] SL-401: http://www.myelomabeacon.com/tag/sl-401/

[21] abstract: http://meetinglibrary.asco.org/content/111442-132

[22] ASCO 2013: http://www.myelomabeacon.com/tag/asco-2013-meeting/

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