Home » News

ASH 2013 Preview: Treatments In Mid- To Late-Stage Clinical Development For Multiple Myeloma

3 Comments By
Published: Nov 20, 2013 8:53 pm

The Beacon continues today with its ‘ASH preview’ series about mye­lo­ma re­search that will be pre­sented at the American Society of Hema­tol­o­gy (ASH) meet­ing in early December.

Abstracts for the ASH presentations are now available, although many contain pre­lim­i­nary information that will be updated at the meet­ing.

The Beacon’s ASH preview articles are intended to highlight the meet­ing's most interesting myeloma-related studies.

The first and second previews, published earlier this week and last week, provide an overview of ASH abstracts about the newest potential mye­lo­ma therapies just starting out in clinical trials.  Further previews will be published in the coming weeks prior to the conference.

Today’s preview continues with the “new treatments” theme, but turns its attention to therapies that are among the furthest in development.   All of the therapies covered below are in at least Phase 2 clinical test­ing, and trial results for these therapies have been discussed at several major medical conferences in the past.

In particular, this article discusses abstracts for ARRY-520 (filanesib), dara­tu­mu­mab, ixazomib (MLN9708), pano­bino­stat, per­i­fo­sine (KRX-0401), and Zolinza (vorinostat).

Many of the results in this preview are promising, but there also are one or two disappointments.

In terms of good news, all of the re­lapsed myeloma patients in a small trial testing the com­bi­na­tion of dara­tu­mu­mab, Revlimid (lenalidomide), and dex­a­meth­a­sone (Deca­dron) responded to treatment, with half achieving a complete or very good partial re­sponse.

The efficacy data for ARRY-520 also look positive.  The two drug com­bi­na­tion of ARRY-520 and Kyprolis (car­filz­o­mib), for example, yields an over­all re­sponse rate comparable to that seen for the well-regarded three-drug com­bi­na­tion of Pomalyst (pomalidomide, Imnovid), Kyprolis, and dex­a­meth­a­sone in a similar patient population.

Similarly, in a trial of ixazomib combined with Revlimid and dex­a­meth­a­sone in newly diagnosed patients, almost all patients responded to the treatment.  The depth of the re­sponses in that trial, however, may not be as significant as may have been hoped.

In terms of not-so-good news, per­i­fo­sine failed to demonstrate efficacy in a Phase 3 study.  In fact, the ad­di­tion of per­i­fo­sine to Velcade (bortezomib) plus dex­a­meth­a­sone therapy resulted in lower re­sponse rates and lower progression-free survival.


Several studies involving ARRY-520 will be presented at this year’s ASH meeting.

ARRY-520 is being developed by Array BioPharma (NASDAQ: ARRY).  The drug inhibits kinesin spindle pro­tein, which plays an important role in actively dividing cells. Initial results for ARRY-520 were presented at last year’s ASH meeting, and they looked promising (see related Beacon news).

Results will be presented from a Phase 2 study of ARRY-520 with or without dex­a­meth­a­sone in patients with heavily pretreated re­lapsed and refractory myeloma (abstract).

The first group of patients (39 percent of the study participants) was treated with ARRY-520 alone; these patients had received a median of six prior lines of therapy.  The second group of patients (61 percent) was treated with ARRY-520 plus dex­a­meth­a­sone; patients in this group had received a median of nine prior lines of therapy.  In both study groups, 16 percent of patients responded to therapy.  Median over­all survival was 19 months for the first group and 11 months for the second group.

This level of single-agent efficacy appears to be in line with – if not greater than – what was seen with the two most recently ap­proved myeloma therapies, Kyprolis and Pomalyst, in their single-agent trials.

Another presentation at ASH will describe the initial findings from a Phase 1 study combining ARRY-520 with Kyprolis for re­lapsed and refractory multiple myeloma (abstract).  The study includes 20 patients who had received a median of four prior lines of therapy.  Among the 19 patients evaluable for re­sponse, the over­all re­sponse rate was 58 percent, with 5 percent achieving a near complete re­sponse, 32 percent a partial re­sponse, and 21 percent a minor re­sponse.  An additional 21 percent achieved stable disease.

The re­sponse rate to this com­bi­na­tion therapy is comparable to what has been seen in a trial testing the com­bi­na­tion of Pomalyst, Kyprolis, and dex­a­meth­a­sone in re­lapsed and refractory patients (see related Beacon news).

An additional presentation at ASH will summarize initial findings of a Phase 1 trial of ARRY-520 in com­bi­na­tion with Velcade (and, in many cases, dex­a­meth­a­sone) in re­lapsed and refractory multiple myeloma patients (abstract). So far, 41 patients who received a median of five prior therapies have been treated with varying doses of ARRY-520 and Velcade.  Although limited results are available at this time, the com­bi­na­tion is registering an over­all re­sponse rate of about 30 percent at the higher doses of ARRY-520.

One potential issue with ARRY-520 going forward may be the fact that, in com­bi­na­tion with drugs such as Kyprolis and Velcade, it tends to noticeably reduce white blood cell counts.  Indeed, in both the Kyprolis and Velcade com­bi­na­tion studies, patients were preventatively given Neupogen (filgrastim) to stimulate their white blood cell production.  Even with that extra safety measure, one patient died in the ARRY-520+Kyprolis trial due to severe fever accompanied by low white blood cell counts (febrile neutropenia).


A presentation at ASH will summarize the initial findings of an ongoing Phase 1/2 trial investigating dara­tu­mu­mab in com­bi­na­tion with Revlimid and dex­a­meth­a­sone in re­lapsed and refractory multiple myeloma patients (abstract).

Daratumumab is being developed by the Danish biotechnology company Genmab together with Janssen Biotech, a Johnson & Johnson (NYSE: JNJ) subsidiary. It is a monoclonal antibody that binds to myeloma cells and then signals the patient's immune system to kill the cells.

Other monoclonal antibodies being tested as potential myeloma therapies include elotuzumabIPH2101, MOR202, and SAR650984.  Daratumumab, MOR202, and SAR650984 are similar in that all three bind to CD38, a protein found on the surface of multiple myeloma and other blood cancer cells.

Daratumab has previously been tested as a single agent in a Phase 1/2 study, with encouraging results (see related Beacon news).

So far, six patients who had received a median of three prior therapies have been recruited for the dara­tu­mu­mab-Revlimid-dex­a­meth­a­sone study. Patients in the trial were permitted to have been treated with Revlimid in the past.  However, if they were previously treated with Revlimid, they must have had at least a min­i­mal re­sponse to the drug.

All patients have responded to the three-drug treatment, which is a very high re­sponse rate for such a group of patients.  Depth of re­sponse also has been promising, with 50 percent of the patients achieving a very good partial re­sponse or complete re­sponse. According to the investigators, side effects have been manageable.


Three presentations will be given at the ASH meeting with clinical trial results for ixazomib (MLN9708).

Ixazomib belongs to the same class of drugs as Velcade and Kyprolis, called proteasome inhibitors. It is being developed by Millennium Pharmaceuticals, the same company that developed Velcade. However, unlike Velcade and Kyprolis, which are given by infusion or injection, ixazomib can be administered orally. Initial results related to ixazomib were presented at the 2011 ASH meeting, and they looked promising (see related Beacon news).

The ixazomib presentation likely to attract the most attention is one describing the results of a Phase 1/2 study of ixazomib in com­bi­na­tion with Revlimid and dex­a­meth­a­sone in newly diagnosed myeloma patients (abstract).  Among 58 patients from Phase 2 of the study who were evaluable for re­sponse, 93 percent responded, with 14 percent achieving a stringent complete re­sponse, 10 percent a complete re­sponse, 43 percent a very good partial re­sponse, and 26 percent a partial re­sponse.

Although the over­all re­sponse rate in this trial was quite high, the depth of re­sponse may dis­ap­point some meet­ing attendees.  The share of patients in the trial who achieved a very good partial re­sponse or better, 67 percent, is the same as was observed in a trial testing Velcade combined with Revlimid and dex­a­meth­a­sone in newly diagnosed patients (see related article in Blood).  The 67 percent share is lower, however, than was seen in a trial testing Kyprolis, Revlimid, and dex­a­meth­a­sone in new­ly diag­nosed patients, where 81 percent of the patients had at least a very good partial re­sponse (see related Beacon news and article in Blood).

The ixazomib, Revlimid, and dex­a­meth­a­sone regimen does appear to have a lower rate of peripheral neuropathy (burning, tingling, or numbness in the hands or feet) than Velcade+Revlimid+dex­a­meth­a­sone (37 percent versus 80 percent, respectively), but the rate is not as low as was observed with the com­bi­na­tion of Kyprolis, Revlimid, and dex­a­meth­a­sone (23 percent).

Initial results will also be presented at ASH for a Phase 2 study of newly diagnosed myeloma patients who underwent stem cell transplantation and then received ixazomib plus Revlimid as maintenance therapy (abstract). So far, 16 patients with a median age of 60 years have been enrolled, and only two have dis­con­tinued maintenance therapy. According to the investigators, the com­bi­na­tion seems to be well tol­er­ated.

A third ixazomib-related presentation will summarize results of a trial investigating the drug as a single agent in re­lapsed myeloma patients who are not resistant to treatment with Velcade (abstract).  This trial enrolled 33 patients with a median of two previous therapies.  Three quarters of the patients had never been treated with Velcade, while the remaining patients had been treated with Velcade, but for no more than six cycles, and not to the point of developing resistance to it.

Patients in the trial initially received treatment with only ixazomib, but dex­a­meth­a­sone could be added if the re­sponse to ixazomib alone was minimal, or if the patients experienced disease progression.

Thus far, the over­all re­sponse rate has been 16 percent among patients treated with ixazomib alone, and 34 percent in those treated with both ixazomib and dex­a­meth­a­sone.


During one of the sessions at ASH, results from a Phase 1/2 study of panobinostat plus Kyprolis will be presented (abstract).

Panobinostat is being developed by the pharmaceutical company Novartis (NYSE: NVS) for a variety of dif­fer­ent cancers.  It belongs to a class of drugs known as oral histone deacetylase (HDAC) inhibitors. Several HDAC inhibitors are being investigated for the treatment of multiple myeloma, including Zolinza, ricolinostat (ACY-1215), and quisinostat.  The drugs in this class work by interrupting cell division and causing cell death. Panobinostat has shown encouraging results in com­bi­na­tion with Velcade and dex­a­meth­a­sone (see related Beacon news).

So far, 44 patients who had received a median of three prior therapies have been treated with one of four different doses. Overall, 64 percent of patients responded, with 31 percent achieving a complete re­sponse or very good partial re­sponse and 30 percent achieving a partial re­sponse.  In addition, the over­all re­sponse rate was 67 percent for patients resistant to previous Velcade therapy and 66 percent for patients resistant to both Velcade and Revlimid therapy.  With a median follow-up time of 6.3 months, the one-year progression-free survival rate was 41 percent and the one-year over­all survival rate was 83 percent.


Researchers at the ASH meeting also will present the results of a terminated Phase 3 study of per­i­fo­sine (KRX-0401) plus Velcade and dex­a­meth­a­sone compared to Velcade plus dex­a­meth­a­sone alone (abstract).

Perifosine is an orally administered drug that belongs to a new class of anti-cancer drugs known as Akt inhibitors.  Akt is a protein believed to play an important role in the development and growth of cancer cells.  Perifsone was being developed by the pharmaceutical company Aeterna Zentaris; however, the company discontinued development of the drug based on preliminary results from this study (see related Beacon news).

The study included 135 re­lapsed and refractory myeloma patients who had received one to four previous lines of therapy and who re­lapsed after previous Velcade therapy.  Perifosine did not improve re­sponse rates or progression-free survival.  The over­all re­sponse rates were 20 percent for the three-drug com­bi­na­tion including per­i­fo­sine, and 27 percent for Velcade plus dex­a­meth­a­sone alone.  Median progression-free survival was 5 months for the per­i­fo­sine com­bi­na­tion and 9 months for Velcade plus dex­a­meth­a­sone.

Perifosine appeared to improve over­all survival, with median over­all survival being 33 months for the per­i­fo­sine com­bi­na­tion and 19 months for Velcade plus dex­a­meth­a­sone, but the improvement was not sta­tis­ti­cal­ly significant.  Therefore, the trial was terminated based on a recommendation from an in­de­pen­dent Data Safety Monitoring Board.


Preliminary results of an ongoing Phase 1/2 study of Zolinza in com­bi­na­tion with Velcade, doxorubicin (Adriamycin), and dex­a­meth­a­sone will be presented at ASH (abstract).

Zolinza (vorinostat), which is marketed by the U.S. pharmaceutical company Merck (NYSE: MRK), is an oral drug already approved in the United States for a certain type of lymphoma. It also is approved for a similar use in Canada and Australia, but not in Europe.

Like panobinostat, Zolinza is an HDAC inhibitor. It has been investigated in various com­bi­na­tions as a po­ten­tial treatment for multiple myeloma and has shown mixed results (see related Beacon news).

The study to be presented at ASH currently includes 18 myeloma patients who had received a median of three prior therapies. Overall, 65 percent of patients responded to the three-drug com­bi­na­tion.  Almost a quarter (22 percent) of patients experienced severe side effects; however, the investigators point out that the observed side effects were in line with the known safety profile of the investigated drugs.

For information about additional studies that will be presented at ASH, see a list of all myeloma-related ASH abstracts, all abstracts about new treatments under development for myeloma, clinical trial results for new treatments, and preclinical research about new treatments.

© 2013 Image copyright Light Knowledge Resources LLC; all rights reserved.
Tags: , , , , , , , , , , , ,

Related Articles:


  • Jan Stafl MD said:

    Thank you Beacon staff for the excellent organization of the over 500 Myeloma related abstracts and posters for the upcoming ASH meeting in New Orleans. The most promising option of treatment for relapsed or refractory MM appears to be daratumumab, with an Imib like lenalidomide, and dex. Further updates on the data will be presented at the meeting, but already the frequent depth of response is impressive.

  • Mark K said:

    Yes, thank you for this data much appreciated.

  • John Pampillonia said:

    A very exciting news article reported by the Associated press gives real hope for all of us with myeloma.

    Go to NBC's website - Go to the News section, and click on the health news.

    Scroll down until you come to an article published Dec. 8th, 2013 titled :

    "Gene Therapy Scores Big Win Against Blood Cancers"

    You will find this article very exciting. There seems to be real hope now for those of us with blood cancers. Myeloma is mentioned along with leukemia as well as some other blood cancers.

    Emjoy this encouraging news ...