This year’s American Society of Hematology (ASH) annual meeting, which is being held in Atlanta, began yesterday and goes through Tuesday.

Today’s myeloma-related presentations began this afternoon with three sessions of oral presentations.  Two of the sessions focused on results from clin­i­cal trials, most of which studied drugs that are still under devel­op­ment as poten­tial treat­ments for multiple myeloma.  The third session, which focused on the biology of myeloma, ran simultaneously with one of the sessions about clin­i­cal trial results.

This article will summarize the first oral session about multiple myeloma treat­ments, which took place from noon to 1:30 in the afternoon.

Although the session was rel­a­tive­ly low-key -- as most medical conference sessions are -- the presenta­tions during the session in­cluded results that are genuinely exciting.

There were results, for example, for three drugs (dara­tu­mu­mab, dinaciclib, and circularly permuted TRAIL) that are sig­nif­i­cantly dif­fer­en­t from any of the drugs cur­rently approved to treat multiple myeloma. That in and of itself is sig­nif­i­cant, because new classes of drugs typically im­prove the treat­ment options avail­able to patients.

Yet, even more im­por­tantly, the study results for these three drugs suggest they have real promise as future myeloma treat­ments.

Similarly, two of the studies that were presented involved com­bi­na­tion treat­ments for heavily pre­treated patients, and the response rates and survival rates for those com­bi­na­tion regi­mens are noticeably higher than what has been seen in the past in this dif­fi­cult-to-treat patient pop­u­la­tion.

Daratumumab

Dr Torben Plesner from Vejle Hospital in Vejle, Denmark, gave the first presentation during the session.  He presented intermediate efficacy results from a Phase 1/2 study of daratumumab in re­lapsed and refractory myeloma patients (abstract; presentation slide deck (pdf) made avail­able by Dr. Plesner as a courtesy to the Beacon’s readers).

Daratumumab is being devel­oped by the Danish pharma­ceu­tical com­pany Genmab together with Janssen Biotech, a Johnson & Johnson (NYSE: JNJ) sub­sid­i­ary.  The drug is a mono­clonal anti­body that binds to the CD38 molecule, which is found on the surface of multiple myeloma and other blood cancer cells.  Once it is bound to the CD38 molecule on cancer cells, dara­tu­mu­mab signals for the immune sys­tem to kill the cells.

The study that Dr. Plesner presented in­cluded 32 heavily pre­treated myeloma patients who had received a median of 6.3 prior treat­ment regi­mens.

During the study, par­tic­i­pants received escalating doses of dara­tu­mu­mab ranging from 0.005 mg/kg to 24 mg/kg.

Of the 32 patients in­cluded in the study, 47 per­cent showed a reduction in the amount of mono­clonal (M) protein in the blood or urine, which corresponded to the fol­low­ing response rates: 13 per­cent of patients achieved a partial response, 19 per­cent a minor response, and 16 per­cent stable disease.

The maximum tolerated dose has not been reached yet.

According to the researchers, dara­tu­mu­mab showed a favorable safety profile.

Pomalidomide Plus Kyprolis And Dexamethasone

The next presentation was given by Dr. Jatin Shah from the M.D. Anderson Cancer Center in Houston.  Dr. Shah presented results from a Phase 1/2 study of pomalidomide in com­bi­na­tion with Kyprolis (car­filz­o­mib) and dexamethasone (Decadron) (abstract; presentation slide deck (pdf) made avail­able by Dr. Shah as a courtesy to the Beacon’s readers).

Pomalidomide is an immuno­modu­la­tory agent, meaning that it works by inducing a patient’s immune sys­tem to attack and destroy myeloma cells. It belongs to the same class of drugs as thalidomide (Thalomid) and Revlimid (lena­lido­mide).

Pomalidomide is being devel­oped by Celgene Corpo­ra­tion (NASDAQ: CELG), the same com­pany that mar­kets Revlimid and thalido­mide in the United States and inter­na­tionally.

The study in­cluded 32 re­lapsed and refractory myeloma patients with a median age of 64 years.  They were a median of five years from diag­nosis and had been treated with a median of six prior lines of ther­apy.

Of the 30 patient evaluable for response, half of the patients responded, with 13 per­cent achieving a very good partial response and 37 per­cent achieving a partial response.

The median pro­gres­sion-free survival was 7.4 months, and at one year, 90 per­cent were alive.

The most common side effects were low white blood cell counts (84 per­cent), low red blood cell counts (63 per­cent), low platelet counts (57 per­cent), and fatigue (56 per­cent).

Revlimid, Thalidomide, And Dexamethasone

Dr. Shah also gave the third talk of the session.  During this presentation, Dr. Shah discussed results from a Phase 1/2 study of Revlimid in com­bi­na­tion with thalido­mide and dexa­meth­a­sone (abstract; presenta­tion slide deck (pdf) made avail­able by Dr. Shah as a courtesy to the Beacon’s readers).

Revlimid and thalido­mide both belong to the same class of drugs known as immuno­modu­la­tory agents.  Typically drugs from dif­fer­en­t classes are admin­istered together to treat myeloma.  Two immuno­modu­la­tory agents have never been studied in com­bi­na­tion before.  However, pre­clin­i­cal studies have shown that thalido­mide can reverse resistance to Revlimid, indicating that it may be beneficial to admin­ister the two drugs together for patients who have re­lapsed or stopped responding to treat­ment.

Dr. Shah reported results from 64 myeloma patients who had been treated with a median of four prior lines of ther­apy.  The median patient age was 65 years.

Among the 61 patients eval­u­ated for response, 51 per­cent responded.  Specifically, 13 per­cent achieved a com­plete or near com­plete response, 7 per­cent achieved a very good partial response, and 31 per­cent achieved a partial response.

Among the 41 patients eval­u­ated who pre­vi­ously did not respond to Revlimid, 34 per­cent responded to the com­bi­na­tion ther­apy, with 5 per­cent achieving a com­plete or near com­plete response, 2 per­cent achieving a very good partial response, and 27 per­cent achieving a partial response.

Median pro­gres­sion-free survival was 8.0 months, and median over­all survival was 29 months.

The most common side effects were fatigue (72 per­cent), shortness of breath (56 per­cent), con­sti­pa­tion (55 per­cent), diarrhea (55 per­cent), low platelet counts (50 per­cent), and low red blood cell counts (47 per­cent).

Dinaciclib

Dr. Shaji Kumar from the Mayo Clinic in Rochester, Minnesota, then discussed results of a Phase 1/2 study of dinaciclib (abstract; presentation slide deck (pdf) made avail­able by Dr.  Kumar as a courtesy to the Beacon’s readers).

Dinaciclib is being devel­oped by Merck (NYSE: MRK).  It is a small molecule that inhibits enzymes called cyclin-dependent kinases, which regulate the cell cycle and are often overactive in cancer cells.  Inhibition of these enzymes and inter­rup­tion of the cell cycle causes the cell to die.

The results are from 27 patients with re­lapsed multiple myeloma who had received a median of four pre­vi­ous lines of ther­apy.

Overall, 15 per­cent responded, with 8 per­cent achieving a very good partial response and 7 per­cent achieving a partial response.

After a median follow-up time of 14.5 months, the pro­gres­sion-free survival rate was 22 per­cent and the over­all survival rate was 44 per­cent.

The most common side effects were diarrhea (74 per­cent of patients), fatigue (52 per­cent), low platelet counts (48 per­cent), and nausea (44 per­cent).

Researchers are planning an upcoming Phase 1 clinical trial that will study dinaciclib in com­bi­na­tion with Velcade (bor­tez­o­mib) and dexa­meth­a­sone.

Pomalidomide Plus Clarithromycin And Dexamethasone

The next presentation was by Dr. Tomer Mark from the Weill Cornell Medical School in New York City.  He spoke about results from a Phase 2 study of poma­lido­mide in com­bi­na­tion with clarithromycin (Biaxin) and dexa­meth­a­sone, a com­bi­na­tion sometimes referred to as ClaPD (abstract;  presentation slide deck (pdf) made avail­able by Dr. Mark as a courtesy to the Beacon’s readers).

Clarithromycin is an antibiotic used to treat bacterial in­fec­tions, and it has been shown to im­prove the anti-myeloma activity of Revlimid and dexa­meth­a­sone.

The study in­cluded 100 myeloma patients who had been treated with a median of five prior lines of ther­apy.  The median age of the patients was 63 years.

Of the 98 patients evaluable for response, 57 per­cent of patients responded, with 6 per­cent achieving a stringent com­plete response, 17 per­cent a very good partial response, and 34 per­cent a partial response.

Median pro­gres­sion-free survival was 8.6 months, and median over­all survival has not yet been reached after a mean follow-up time of 9.6 months.

The most common severe side effects were low white blood cell counts (47 per­cent), low platelet counts (27 per­cent), and low red blood cell counts (25 per­cent).

Circularly Permuted TRAIL

The session concluded with a talk by Dr. Wenming Chen from the Chaoyang Hospital of Capital Medical University in Beijing.  Dr. Chen presented results of a Phase 2 study of circularly permuted TRAIL (abstract).

Circularly Permuted TRAIL (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 that cause cells to die.  Preclinical studies have shown that CPT kills cancers cells but not most healthy cells.

The study in­cluded 27 people with re­lapsed or refractory multiple myeloma who had been treated with a median of three prior lines of ther­apy.  The median patient age was 59 years.

Overall, 33 per­cent of the study par­tic­i­pants responded to CPT treat­ment, in­clud­ing 4 per­cent who achieved a near com­plete response and 30 per­cent who achieved a partial response.

The most common side effects were fever (48 per­cent), elevated liver enzymes (41 per­cent), and low white blood cell counts (26 per­cent).

Myeloma presentations from the rest of Day 2 as well as 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.