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ASH 2012 Multiple Myeloma Update – Day One: Poster Sessions

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Published: Dec 9, 2012 6:50 am

Yesterday was the first day of research presentations at this year’s American Society of Hematology (ASH) annual meeting, which is being held in Atlanta.

Research findings related to multiple myeloma was presented in three different sessions during the day.

Two of the sessions were actually the same general educational session about multiple myeloma, repeated at two different times during the day. The Beacon will cover the presentations given during those sessions in a separate daily update.

The key myeloma-related research presented yesterday, however, was made public during a poster session in the early evening.

During the session, research results were made available for review by meeting attendees in the form of posters, each of which summarized the results of a single study. As is typically the case during such sessions, each poster was about two feet high by three or four feet in length. All the posters — of which there were literally hundreds — were displayed in an exhibit hall covering an area larger than a football field.

The findings from the key myeloma-related posters that were on display last night are summarized below.

New Myeloma Treatments

One poster included results from a Phase 1b study of Circularly Permuted TRAIL (CPT) (abstract). CPT is being developed by Beijing Sunbio Biotech as a treatment for multiple myeloma and other blood cancers.  It activates receptors in the body called TRAIL, which cause cells to die.  Preclinical studies have shown that CPT kills cancers cells but not most healthy cells.

In the Phase 1b study, 29 relapsed/refractory myeloma patients with a median age of 57 years were treated with 5 mg/kg to 15 mg/kg of CPT and then evaluated for response.  The study participants had received a median of four prior therapies.

Among the patients treated with at least 8 mg/kg of CPT, 17 percent to 33 percent of the patients responded, which, according to the investigators, indicates that the optimal CPT dose is between 8 mg/kg and 15 mg/kg.

The researchers concluded from the results of the study that CPT was well tolerated up to a dose of 15 mg/kg. The most commonly observed side effect included fever (21 percent of patients), low white blood cell counts (17 percent), fatigue (14 percent), and vomiting (10 percent).

Another poster included the results of a Phase 1 study of MLN8237 and Velcade (bortezomib) in relapsed and refractory multiple myeloma patients (abstract). MLN8237 is being developed by Millennium Pharmaceuticals, the same company that developed Velcade and markets it in the United States. MLN8237 inhibits the activity of the enzyme aurora kinase, which plays a crucial role in cell division.

The study included 19 patients with a median age of 64 years. All patients must have had between one and four prior therapies to be able to participate in the trial.

The patients received 20 mg to 50 mg of oral MLN8237 twice daily on days 1 to 7 plus 1.5 mg/m2 of intravenous Velcade weekly in a 28-day treatment cycle.

Overall, 26 percent of patients responded to treatment, with 5 percent achieving a complete response, 5 percent achieving a very good partial response, and 16 percent achieving a partial response.

The most commonly observed side effects included peripheral neuropathy (pain and tingling in the extremities, 63 percent of patients), fatigue (63 percent), diarrhea (53 percent), and nausea (47 percent).

The researchers pointed out that the treatment regimen used during the study did not include a steroid, such as dexamethasone (Decadron) or prednisone, and that only patient has discontinued treatment due to side effects.

The researchers have already initiated a Phase 2 study of the combination.

Another poster presented results from a Phase 1 study of veliparib in combination with Velcade and dexametheasone in relapsed / refractory myeloma patients (abstract).

Veliparib, which is being developed by Abbott, is a potential anti-cancer drug that inhibits the activity of the enzymes PARP1 and PARP2. It is being studied as a treatment for a variety of different cancers.

The Phase 1 study included 15 patients with a median age of 61 years. The patients had received a median of three prior lines of therapy. Patients received 20 mg to 100 mg of oral veliparib twice daily for 14 days in combination with Velcade and dexamethasone.

Of the 11 patients evaluable for response, 46 percent of patients achieved a partial response or better, which the researchers described as significant.

The most common severe side effects included low platelet counts (38 percent of patients), low red blood cell counts (13 percent), and diarrhea (13 percent). In addition, 38 percent of patients experienced mild peripheral neuropathy.

Another poster summarized the results of a Phase 2 study of Bexxar (iodione-131 tositumomab) in multiple myeloma patients (abstract). Bexxar is currently approved in the United States for the treatment of non-Hodgkins’ lymphoma and is being marketed and further developed by GlaxoSmithKline.

The study included 16 myeloma patients with a median age of 56 years who had received a median of two prior therapies. All patients were in stable disease when they entered the study.

Overall, 31 percent of patients responded to Bexxar treatment. The researchers found that significantly more patients (67 percent) who carried the CD20 protein on the surface of their myeloma cells responded to Bexxar treatment, compared to patients who did not carry the CD20 protein on the surface of their cells (10 percent).

The most frequently observed severe side effects included low white blood cell counts (44 percent of patients), low platelet counts (25 percent), and infections (13 percent).

Combination Therapies

Yesterday’s poster session also featured posters that examined combinations of therapies already approved for the treatment of multiple myeloma.

In one poster, Japanese researchers summarized the results of a study involving a treatment regimen combining lower doses of Velcade, cyclophosphamide (Cytoxan), and dexamethasone, commonly abbreviated as CyBorD, in both newly diagnosed and relapsed / refractory myeloma patients (abstract).

The study included 20 patients with a median age of 72 years who were not eligible for stem cell transplantation.

The researchers found that the low-dose version of CyBorD showed similarly high efficacy as the standard-dose combination; 90 percent of patients responded to the lower-dose therapy, with 40 percent achieving a complete or near complete response, 25 percent a very good partial response, and 25 percent a partial response.

In addition, the low-dose regimen was associated with lower rates of side effects — in particular peripheral neuropathy, a common side effect of Velcade therapy. Only 15 percent of the patients experienced peripheral neuropathy, and none of the patients discontinued treatment due to peripheral neuropathy.

Based on their findings, the researchers conclude that low-dose CyBorD may be a good treatment option for elderly and frail myeloma patients.

Another poster summarized the results of a Dutch study that shows that the combination of Revlimid (lenalidomide), Velcade, and dexamethasone followed by Revlimid maintenance is effective and safe in myeloma patients at first relapse (abstract).

The Phase 2 study included 74 patients with a median age of 66 years.

Eighty-eight percent of patients responded to the treatment within a median of 1.1 treatment cycles.  In particular, 27 percent of patients achieved a complete response, 37 percent a very good partial response, and 24 percent a partial response.

The median progression-free survival time was 18 months, and at 30 months, the overall survival rate was 65 percent.

Twenty-two percent of patients experienced severe blood-related side effects, and 17 percent experienced severe peripheral neuropathy.

Another poster presented the results of a Phase 1/2 study that sought to establish a safe and effective dose of Revlimid in combination with dexamethasone in multiple myeloma patients with kidney impairment (abstract). Revlimid is not frequently used in patients with kidney impairment because it is excreted through the kidneys.

The study included 26 multiple myeloma patients with kidney impairment. The median patient age was 73 years. Depending on their kidney function, the patients received between 5 mg and 25 mg of Revlimid daily or every other day.

Overall, 56 percent of patients responded to the treatment, with 4 percent achieving a complete response, 8 percent a very good partial response, and 44 percent a partial response.

According to the investigators, the treatment was well tolerated, although 70 percent of patients experienced severe side effects.

The maximum tolerated dose has not been reached yet, which, according to the investigators, allows Revlimid to be given at higher doses than previously thought.

MGUS And Smoldering Myeloma

The poster session yesterday evening included several studies on the myeloma precursor diseases monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma.

One poster summarized results of a small study conducted at the National Institutes of Health showing that 20 percent of untreated patients with MGUS and smoldering myeloma had early signs of dysfunctional blood cell production, which is normally seen in patients with a condition called myelodysplastic syndromes (MDS) (abstract).

According to the researchers, their findings further support the theory that there may be a biological link between plasma cell disorders (such as MGUS, smoldering myeloma, and multiple myeloma) and MDS even before the onset of plasma cell disorders and exposure to treatment.

Another poster presented results of a German study that investigated the influence of chromosomal abnormalities on the risk of progression in smoldering myeloma patients (abstract). The median time to progression for all 231 smoldering myeloma patients included in the study was 4.9 years.

The researchers found that the time to disease progression was significantly shorter for patients with the chromosomal abnormalities del(17p13) (2.7 years), t(4;14) (2.9 years), and +1q21 (3.7 years).

Biomarkers

Several studies investigated the role of various biomarkers in multiple myeloma.

One poster summarized the findings of an Australian study showing that multiple myeloma patients who survive for 10 years have higher than normal levels of certain types of T cells (abstract).

T cells are a type of white blood cell that make up a key part of the immune system. In particular, the researchers found that long-term survivors had T cells that were not anergic, meaning that more likely than usual to activate the body’s defense mechanisms against myeloma cells. According to the investigators, these cells may be candidates for restoring immunological control of multiple myeloma.

Another poster summarized the results of a Japanese study that indicates that the protein interleukin-2 may serve as a marker to identify patients who develop Velcade-induced peripheral neuropathy (abstract). The researchers found that patients who showed increased levels of interleukin-2 before Velcade therapy were more likely to develop peripheral neuropathy.

Another poster displayed the findings of a German study that showed that the amount of the protein cereblon varies depending on the form of plasma cell disorder patients have (abstract). Previous studies have shown that cereblon is necessary for the immunomodulatory drugs, Revlimid and pomalidomide in particular, to be effective against multiple myeloma.

The German researchers found that patients with MGUS had higher levels of cereblon in their blood than patients with active myeloma. Among patients with chromosomal abnormalities, those with del17p13 and gains at 1q21 showed the lowest levels of cereblon.

Myeloma presentations from Day 2, Day 3, and Day 4 of the ASH 2012 meeting also will be summarized in ASH daily updates to be published at The Beacon the next few days.  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 ASH meeting, see The Beacon’s full ASH 2012 coverage.

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2 Comments »

  • David Finkelstein said:

    Great summary! Thanks for this.

    One of the links needs to be added. The abstract for the study below is missing

    Another poster presented the results of a Phase 1/2 study that sought to establish a safe and effective dose of Revlimid in combination with dexamethasone in multiple myeloma patients with kidney impairment (abstract). Revlimid is not frequently used in patients with kidney impairment because it is excreted through the kidneys.

    David

  • Maike Haehle said:

    Thank you very much, David, for pointing that out. The link has been added.