Yesterday was the sec­ond day of the 2012 American Society of He­ma­tol­ogy (ASH) annual meeting, which is being held in Atlanta.

The day's myeloma-related pre­sen­ta­tions began in the 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 being devel­oped for the treat­ment of mul­ti­ple myeloma.  The third session, which focused on the biology of myeloma, ran simultaneously with one of the sessions about clin­i­cal trial re­­sults.

An up­date pub­lished yes­ter­day evening summarized the re­­sults for the first oral session about mul­ti­ple myeloma treat­ments (see re­lated Beacon ^[1] news).  This article will summarize the highlights from the sec­ond oral session about myeloma treat­ments.

The sec­ond session kicked off with two pre­sen­ta­tions involving treat­ment regi­mens that in­clude main­te­nance ther­apy with thalido­mide.  These re­­sults are likely to be of pri­mary interest to Beacon readers outside of the U.S., where thalido­mide main­te­nance ther­apy is used much more fre­quently than in the U.S.

Three of the pre­sen­ta­tions from the late afternoon session con­cerned new myeloma ther­a­pies still under de­vel­op­ment.   The pre­sen­ta­tions about poma­lido­mide and elotuzumab made clear why there is sig­nif­i­cant interest in those drugs.  Results for the third drug in the group, oprozomib, were based on a trial that cur­rently has only a small num­ber of patients; the re­­sults, how­ever, sug­gest that side effects may be an issue with the drug.

Thalidomide Maintenance

Dr. Annamaria Brioli from the In­sti­tute of Cancer Re­search in London pre­sented the re­­sults from a study com­par­ing thalidomide ^[2] (Thalomid) main­te­nance ther­apy versus no main­te­nance ther­apy (abstract ^[3]). The re­­sults were part of a larger study which has been reported about extensively in the past.

The study in­cluded 818 mul­ti­ple myeloma patients of whom 408 re­ceived thalido­mide main­te­nance ther­apy and 410 re­ceived a placebo.

The median pro­gres­sion-free sur­vival time was 23 months for those in the thalido­mide main­te­nance group and 15 months for those who re­ceived a placebo.  The median over­all sur­vival times were 59 months and 58 months, re­spec­tively.

Dr. Brioli then reported that standard-risk patients who re­ceived thalido­mide main­te­nance had sig­nif­i­cantly longer pro­gres­sion-free sur­vival than those who re­ceived no main­te­nance (30 months and 20 months, re­spec­tively).  High-risk patients had similar pro­gres­sion-free sur­vival re­gard­less of whether they re­ceived main­te­nance ther­apy (11 months and 13 months, re­spec­tively), but their over­all sur­vival was neg­a­tively affected if they re­ceived thalido­mide main­te­nance ther­apy (35 months versus not yet reached).  Patients classified as ultra-high risk had poor pro­gres­sion-free and over­all sur­vival, re­gard­less of whether they re­ceived main­te­nance ther­apy.

Thalidomide main­te­nance appeared to im­prove pro­gres­sion-free sur­vival of patients who did not have the chromosomal ab­nor­mal­ity t(4;14) or who had t(4;14) but no addi­tional chromosomal ab­nor­mal­i­ties.

Patients with one or more extra chromosomes also appeared to gain a pro­gres­sion-free sur­vival ben­e­fit from thalido­mide main­te­nance.

VMPT-VT Versus VMP

The sec­ond pre­sen­ta­tion was given by Dr. Antonio Palumbo from the Uni­ver­sity of Torino in Italy.  Dr. Palumbo pre­sented four-year sur­vival re­­sults from a Phase 3 study com­par­ing two Velcade-based regi­mens (abstract ^[4]; pre­sen­ta­tion slide deck ^[5] made avail­able by Dr. Palumbo as a courtesy to the Beacon's readers).

The study in­cluded 511 newly diag­nosed mul­ti­ple myeloma patients with a median age of 71 years.

Half of the patients re­ceived initial ther­apy with Velcade ^[6] (bor­tez­o­mib), melphalan ^[7] (Alkeran), prednisone ^[8], and thalido­mide followed by main­te­nance ther­apy with Velcade and thalido­mide, known as VMPT-VT.  The other half re­ceived only initial ther­apy with Velcade, mel­phalan, and pred­ni­sone, known as VMP.

After a median follow-up of nearly four years, the median over­all sur­vival of the VMPT-VT group was not yet reached, as com­pared to 61 months for the VMP group.

Dr. Palumbo esti­mated that five years after the start of treat­ment, 61 per­cent of the VMPT-VT group would be alive, as com­pared to 51 per­cent of the VMP group.  He noted that patients younger than 75 years of age and patients who achieved a com­plete re­sponse after their initial ther­apy ben­e­fitted the most from the VMPT-VT ther­apy.

Among those who re­ceived main­te­nance ther­apy, the most common severe side effects were periph­eral neu­rop­athy (4 per­cent), blood-related side effects (3 per­cent), and in­fec­tion (1 per­cent).

Pomalidomide Plus Dexa­meth­a­sone

The next three pre­sen­ta­tions were about new drugs being devel­oped for the treat­ment of mul­ti­ple myeloma.  First, Dr. Martha Lacy from the Mayo Clinic in Rochester, Minnesota, pre­sented long-term follow-up re­­sults from six Phase 2 stud­ies of pomalidomide ^[9] plus dexamethasone ^[10] (Decadron) (abstract ^[11]; presentation slide deck ^[12] (pdf) made avail­able by Dr. Lacy 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 ^[13] (Thalomid) and Revlimid ^[14] (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 stud­ies in­cluded 344 myeloma patients who were a median of 4.4 years from their myeloma diag­nosis and who had been treated with a median of three prior ther­a­pies.  The median patient age was 64 years.

Overall, 35 per­cent of patients responded to the treat­ment, with 5 per­cent achieving a com­plete re­sponse, 12 a very good partial re­sponse, and 18 a partial re­sponse. The strongest predictor or re­sponse was the num­ber and type of pre­vi­ous ther­a­pies.

After a median follow-up of 10.4 months, 62 per­cent of patients are alive and 30 per­cent have not yet progressed.  The strongest predictor for time to pro­gres­sion and sur­vival were the num­ber and type of pre­vi­ous ther­a­pies, LDH levels and beta-2 microglobulin levels.

Severe side effects in­cluded low white blood cell counts (50 per­cent), low red blood cell counts (17 per­cent), low platelet counts (13 per­cent), pneu­monia (9 per­cent), and fatigue (8 per­cent).  In addi­tion, 3 per­cent of patients devel­oped blood clots in the vein.

Elotuzumab Plus Revlimid And Dexa­meth­a­sone

Next, Dr. Paul Richardson from the Dana-Farber Cancer In­sti­tute in Boston pre­sented re­­sults from a Phase 2 study of elotuzumab ^[15] in com­bi­na­tion with Revlimid and dexa­meth­a­sone (abstract ^[16]; presentation slide deck ^[17] made avail­able by Dr. Richardson as a courtesy to the Beacon's readers).

Elotuzumab, which is being devel­oped by Bristol-Myers Squibb (NYSE: BMY) and Abbott (NYSE: ABT), belongs to a class of drugs 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.  Other com­pounds in this class of drugs in­clude daratumumab ^[18] and siltuximab ^[19], which are in earlier phases of clin­i­cal de­vel­op­ment than elotuzumab.

The study in­cluded 73 myeloma patients treated with a median of two prior lines of ther­apy.  The median patient age was 63 years.

Half of the study par­tic­i­pants re­ceived 10 mg/kg of elotuzumab, while the other half re­ceived 20 mg/kg of the drug.

The re­­sults showed that the out­comes of those treated with 10 mg/kg of elotuzumab were better than the out­comes of those treated with 20 mg/kg.

In par­tic­u­lar, 92 per­cent of the patients in the 10 mg/kg group responded to treat­ment, as com­pared to 76 per­cent in the 20 mg/kg group.

After a median follow-up of 21 months, median pro­gres­sion-free sur­vival has not been reached yet for the 10 mg/kg group and 19 months for the 20 mg/kg group.

Two-thirds of the patients ex­peri­enced at least one severe or life-threatening side effect.  The most common were low blood cell counts (10 per­cent to 20 per­cent).

The com­bi­na­tion using 10 mg/kg of elotuzumab is being fur­ther studied in Phase 3 stud­ies of newly diag­nosed myeloma patients.

Oprozomib

Dr. Michael Savona from the Sarah Cannon Re­search In­sti­tute in Nashville, Tennessee, then discussed re­­sults of a Phase 1b study of oprozomib ^[20] (abstract ^[21]).

Oprozomib is being devel­oped by Onyx Pharma­ceu­ticals (NASDAQ: ONXX), the com­pany that mar­kets Kyprolis ^[22] (car­filz­o­mib).

Oprozomib is chemically very similar to Kyprolis, and also works similarly to Velcade.  All three of these drugs belong to the class of drugs known as pro­te­a­some in­hib­i­tors.  They work by preventing the breakdown of pro­tein in cancer cells, triggering their death.  Oprozomib, unlike Kyprolis and Velcade, can be taken orally.

Oprozomib is cur­rently being in­ves­ti­gated as a treat­ment for solid tumors as well as blood cancers.

Dr. Savona pre­sented initial re­­sults from 13 people with blood cancers who re­ceived be­tween 120 mg and 210 mg of oprozomib per day.  The study par­tic­i­pants had re­ceived a median of four pre­vi­ous treat­ment regi­mens.

Of the 10 patients eval­u­ated for re­sponse, nine achieved at least stable dis­ease.  Two patients with mul­ti­ple myeloma achieved a partial re­sponse and a minimal re­sponse.  An addi­tional patient with chronic lym­pho­cytic leukemia achieved a partial re­sponse.

The most common side effects were diarrhea (78 per­cent), nausea (78 per­cent), and vomiting (67 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 ^[23] coverage.