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ASH 2013 Preview: The Newest Multiple Myeloma Treatments On The Horizon

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Published: Nov 15, 2013 10:52 pm

At this year’s American Society of Hematology (ASH) meeting, which will be held in early December, more than 100 oral presentations and about 400 poster pre­sen­ta­tions will summarize research focused on multiple myeloma.

Abstracts for these presentations are now available.

During the next several weeks, The Beacon will publish a series of arti­cles pre­viewing the myeloma-related studies from the ASH meeting that are of par­tic­u­lar interest.

Each of the articles will cover abstracts related to a specific topic, such as new treatments under de­vel­op­ment, current treatments, stem cell trans­plan­ta­tion, prognostic factors, and the myeloma precursor dis­eases monoclonal gammopathy of un­de­ter­mined significance (MGUS) and smoldering multiple myeloma.

In today's preview article, The Beacon takes a look at the ASH abstracts that report clinical trial results for a special group of potential new myeloma treatments.  The treatments covered in today's article are "special" in the sense that they are among the newest potential myeloma therapies being tested in clinical trials.

In particular, studies involving a total of eight new treatments are covered in this article, including afuresertib (GSK2110183), AT7519M, CUDC-907, IPH 2101, KW-2478, LGH447, NOX-A12, and SAR650984.

The results reported for each drug are based on the preliminary data available in the meeting abstracts.  The drugs with results that seem particularly noteworthy are discussed first in the abstract summaries below.

Before turning to those summaries, it is worth noting that there are two very positive aspects to the studies as a whole.

One is the simple fact that this article – which focuses solely on drugs in the very earliest stages of clinical trial testing – is able to report results for as many as eight different potential new myeloma treatments.  Not two or three.  Eight.

The second positive aspect of the studies discussed below is that the drugs they are chemically dif­fer­ent from one another and from existing myeloma therapies such as Revlimid (lenalidomide) and Vel­cade (bor­tez­o­mib).

This means that the treatments reviewed below offer potential new avenues for the treatment of myeloma, which would provide patients and their physicians with genuinely new options for treating the disease.

Now, this positive news needs to be balanced with the fact that, at this stage, it is difficult to assess exactly how promising these newest treatments are.  Many of the results below, for example, are from Phase 1 trials.  Such trials usually involve a small number of patients, and they focus on testing different doses of a drug to determine its safety and the best dose to use in later trials.

As a result, the response rates seen in Phase 1 trials are quite variable and generally lower than those seen in later (Phase 2 and Phase 3) clinical trials.

So the good news, represented by the sheer number and diversity of the treatments discussed below, needs to be tempered with the realization that researchers are just beginning to understand exactly how promising these new drugs are.

Afuresertib

One of the presentations to be made at this year’s ASH meeting will summarize the results of a Phase 1b study of afuresertib (GSK2110183) in combination with Velcade and dexamethasone (Decadron) for the treatment of relapsed and refractory myeloma (abstract).

Afuresertib, which is being developed by the pharmaceutical company GlaxoSmithKline (NYSE: GSK), be­longs to a 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.  Another Akt inhibitor that has been tested as a potential myeloma therapy is perifosine.

The Phase 1b trial for afuresertib combined with Velcade and dexamethasone includes 67 myeloma pa­tients who had been treated with a median of 3.5 prior lines of therapy.  Most patients had been treated with both proteasome inhibitors (such as Velcade) and immunomodulatory agents (such as Revlimid), with some of the patients being resistant to one or both of those classes of drugs.  The overall response rate was 41 percent, with 3 percent of the patients achieving a complete response, 9 percent a very good partial response, and 29 percent a partial response.

Among patients treated at the maximum tolerated dose of 150 mg of afuresertib, 61 percent responded. However, none of these patients were resistant to previous Velcade therapy.

AT7519M

Results from a Phase 1/2 study to be presented at the ASH meeting will show that AT7519M did not have significant activity in relapsed and refractory myeloma patients when used alone.  However, it was clearly active when used in combination with Velcade (abstract).

AT7519M, which is being developed by Astex Pharmaceuticals (NASDAQ: ASTX), is a cyclin-dependent kinase inhibitor; it blocks enzymes that are needed for cells to divide.

In part one of the study, nine patients with relapsed or refractory myeloma were treated with AT7519M alone. The treatment was well tolerated, but no patients responded (although at least one experienced stable disease).

In part two of the study, nine patients who had been treated with a median of five prior lines of therapy were treated with AT7519M plus Velcade.  Overall, 33 percent of patients responded to the combination, with 11 percent achieving a very good partial response and 22 percent achieving a partial response.

NOX-A12

A Phase 2a study of NOX-A12 in combination with Velcade and dexamethasone will also be presented at ASH (abstract).

NOX-A12 is being developed by Noxxon Pharma.  NOX-A12 binds to a small molecule called CXCL12 that is known to play a role in drug resistance.

So far, 21 patients who had received a median of two prior lines of therapy have been enrolled in the trial.  Among the nine patients evaluated for response, 67 percent responded to the combination of NOX-A12, Velcade, and dexamethasone, with 22 percent achieving a very good partial response and 44 percent achieving a partial response.

KW-2478

Researchers will present results from a Phase 1/2 study of KW-2478 plus Velcade for the treatment of re­lapsed and refractory myeloma (abstract).

KW-2478 belongs to a class of anti-myeloma drugs called Hsp90 inhibitors. The drug is being developed by the Japanese drug manufacturer Kyowa Hakko Kirin. Other Hsp90 inhibitors that have been investigated as potential myeloma treatments include ganetespib and tanespimycin.

The KW-2478 study included 95 patients (15 patients in Phase 1 and 80 patients in Phase 2) who had received one to three prior treatment regimens; none of the patients were resistant to prior Velcade therapy.  Among the 79 patients from Phase 2 of the study who were evaluated for response, 39 percent responded, with 4 percent achieving a complete response, 14 percent a very good partial response, and 22 percent a partial response.  Median progression-free survival was 6 months.

IPH2101

Another presentation at the ASH meeting will summarize results from a Phase 1 study of IPH2101 plus Revlimid in relapsed myeloma patients (abstract).

IPH2101, which is being developed by Innate Pharma, belongs to the same broad class of drugs as elo­tu­zu­mab and daratumumab, called monoclonal antibodies. Monoclonal antibodies work by identifying proteins on the surface of myeloma cells and signal­ing for the immune system to destroy the cancer cells.  Specifically, IPH2101 activates anti-tumor immune cells known as natural killer cells.

The study includes 15 relapsed myeloma patients who had received one or two previous lines of therapy.  Patients could participate in the trial if they had previously been treated with Revlimid, but not if their disease was considered resistant to Revlimid therapy.

Overall, the response rate was 33 percent, with 13 percent of the patients achieving a very good partial response and 20 percent achieving a partial response.  The median duration of response was at least 15 months.

SAR650984

Also on the agenda for the ASH meeting will be a presentation about another monoclonal antibody, SAR650984.  In particular, researchers will present results of a Phase 1 study of the drug in patients with relapsed or refractory myeloma or another blood cancer (abstract).

SAR650984 is being developed by the pharmaceutical company Sanofi-Aventis.  The Phase 1 study of the drug includes 32 blood cancer patients who were diagnosed a median of 6.8 years before study par­tic­i­pa­tion.  Overall, 16 percent of patients achieved a partial response.  Higher doses of SAR650964 are still being tested.

LGH447

Results of a Phase 1 study of LGH447 in relapsed and refractory myeloma will also be presented at the meeting (abstract).

LGH447 inhibits an enzyme in cancer cells known as PIM kinase, thereby disrupting the cell division cycle and causing cancer cell death.  The drug is being developed by the pharmaceutical company Novartis (NYSE: NVS).

In their abstract for the ASH meeting, the investigators involved in the Phase 1 LGH447 trial report that, among the 19 patients treated so far, multiple patients have responded and the best response has been a very good partial response.

CUDC-907

Also at ASH, initial results will be presented from a Phase 1 study of CUDC-907 in patients with relapsed or refractory multiple myeloma or lymphoma (abstract).

CUDC-907, which is being developed by the pharmaceutical company Curis (NASDAQ:CRIS), is a multi-targeted agent that inhibits both PI3K and histone deacetylase (HDAC) in cancer cells.

Other HDAC inhibitors that are being investigated as potential treat­ments for multiple myeloma include Zolinza (vorinostat), panobinostat, and ricolinostat (ACY-1215).

At the time of initial analysis, the study included 6 patients who had received a median of three prior treatment regimens; 33 percent of the patients had multiple myeloma.  No response results are available yet.

Additional New Therapies Being Studied For Multiple Myeloma

Researchers at the ASH meting also will present results for studies involving several other new agents being studied for the treatment of multiple myeloma, including CC-122 (abstract), Cialis (tadalafil) (abstract), PAT-SM6 (abstract), Reolysin (abstract), SNS01-T (abstract), and tivantinib (ARQ197) (abstract).  However, the results for these drugs are not yet particularly promising, with the best responses being stable disease.

In most of these cases, the drugs were tested as single agents.  Some of these drugs, such as SNS01-T, are still being tested at higher doses.  Others, such as CC-122, were tested in patients with a variety of can­cers, so the number of myeloma patients was small.  Many of these other drugs may turn out be effective if administered in combination with other anti-myeloma drugs.  Cialis was added to Revlimid-based reg­i­mens to which patients had previously failed to respond; however, it did not re-sensitize patients to their prior regimens.

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.

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3 Comments »

  • Mark K said:

    Thank you very much,this is very positive and promising data.

  • Anne Huntington said:

    After chemos Revlimid, Velcade, carfilzomib (most successful) and finally, Pomalyst, what would be the next med or meds used for MM?

  • Myeloma Beacon Staff said:

    Hi Anne,

    We think it would be best if you posted this question to the forum, providing a bit more information about your treatment history and how you responded to the different treatments. You're likely to get better advice in that case. (Also, remember that registration is not required to view postings in the forum or to make postings there.)

    Best of luck to you.