The American Society of Clinical Oncology will hold its 50^th annual meet­ing May 30 through June 3 in Chicago.

Similar to pre­vi­ous years, more than 25,000 physicians and re­searchers from all over the world are ex­pec­ted to attend the five-day meeting to dis­cuss the current re­search in cancer treat­ment and care.

During the meeting, there will be pre­sen­ta­tions about all areas of cancer, in­clud­ing many focused specifically on multiple myeloma. The ASCO website cur­rently lists in­for­ma­tion about more than 60 myeloma-related studies (included under either the "multiple myeloma" or "plasma cell disorders” at the website for the ASCO abstracts).

The ASCO meeting is one of three annual scientific meetings where im­por­tant new myeloma-related re­search findings are reported. The other two key conferences are the annual meetings of the American So­ci­e­ty of Hematology (ASH) and the European Hematology Association (EHA).

As in pre­vi­ous years, The Myeloma Beacon will be covering the ASCO 2014 meeting in detail.  Readers can ex­pec­t a number of articles during and after the meeting about the key myeloma findings.

A Quick Take On The Meeting

One of the reasons ASCO’s annual meeting is held in Chicago every year is that few other U.S. cities have convention facilities large enough to host a meeting of ASCO’s size.

Yet, despite ASCO’s over­all size, the amount of myeloma-related re­search pre­sented at the meeting is usu­al­ly much lower than at the somewhat smaller, but more focused, American Society of Hematology (ASH) meeting held each De­cem­ber.

This year is no exception.  The number of myeloma-related pre­sen­ta­tions that will take place at the 2014 ASCO meeting is only about an eighth of the number of myeloma-related pre­sen­ta­tions that were made at the ASH meeting last De­cem­ber.

Nevertheless, there are still a number of im­por­tant myeloma-related pre­sen­ta­tions that will take place at this year’s ASCO meeting.  The myeloma-related highlights of the meeting are as follows:

First, results will be pre­sented for a key trial involving panobinostat.  These results were first announced, in qualitative terms, in a press release put out last De­cem­ber by Novartis, the com­pany devel­op­ing pano­bino­stat.  The quantitative results to be pre­sented at ASCO bode well for panobinostat’s chances to be approved in a year or two in both the U.S. and Europe as a new treat­ment for multiple myeloma.

Second, trial results for daratumumab and SAR650984 will be pre­sented that in­di­cate that both drugs con­tin­ue to show sub­stan­tial anti-myeloma ther­apy.

Third, two studies will be pre­sented that shed light on the rel­a­tive­ efficacy and safety of Revlimid and tha­lido­mide when they are used in com­bi­na­tion with other drugs to treat newly diag­nosed multiple myeloma.

Revlimid and thalido­mide are chemically related to one another.  Until recently, how­ever, there has been only limited in­for­ma­tion avail­able to make reliable comparisons of the two drugs.

Fourth, ASCO will feature results from several studies that provide new insights into which smol­der­ing mye­lo­ma patients may be particularly likely to progress to active (symptomatic) multiple myeloma.

Results also will be pre­sented for studies in­ves­ti­gated several other new – or recently approved – myeloma ther­a­pies in re­lapsed myeloma patients.

In addi­tion, a key pre­sen­ta­tion will share the first results of a new study looking at the poten­tial benefit of con­tin­uous ther­apy for newly diag­nosed myeloma patients.

Organization Of The Meeting

Research findings pre­sented at ASCO and other scientific meetings are generally communicated in either oral pre­sen­ta­tions or poster summaries.

Oral pre­sen­ta­tions are usually given for re­search that is con­sidered particularly im­por­tant, either because the subject itself is im­por­tant or the results are based on sub­stan­tial amounts of evi­dence (for example, a sizable clin­i­cal trial).

Poster re­search summaries are made avail­able during specific “poster sessions,” when re­searchers dis­play summaries of their studies on posters in a large exhibition hall.

Compared to the re­search summarized during oral pre­sen­ta­tions, the findings in poster summaries gen­er­al­ly are in earlier stages of devel­op­ment and may in­volve­ only laboratory re­search or clin­i­cal trials with just a small number of patients.

Abstracts for all ASCO pre­sen­ta­tions are now avail­able and can be searched at this web page.  However, the results in some abstracts are pre­lim­i­nary and will be updated at the meeting.  In addi­tion, there also will be two education sessions at the meeting (on Friday May 30 and Monday, June 2), during which broad over­views of myeloma-related re­search will be pre­sented.

In the rest of this article, we provide addi­tional detail about the most im­por­tant myeloma-related studies that will be pre­sented at the meeting.  During and after ASCO, we will provide more in-depth summaries of these studies that in­clude the updated data pre­sented during the meeting.

Panobinostat

One of the most im­por­tant myeloma-related pre­sen­ta­tions at the ASCO meeting will be the first to be given during the only session of oral pre­sen­ta­tions during the conference.

On June 2, Dr. Paul Richardson from the Dana-Farber Cancer Center in Boston will present initial results from a Phase 3 study eval­u­ating the safety and efficacy of panobinostat plus Velcade (bor­tez­o­mib) and dexa­metha­sone (Decadron) versus Velcade and dexa­meth­a­sone alone in re­lapsed or re­lapsed and re­frac­tory multiple myeloma (abstract).

The study results in­di­cate that adding panobinostat to Velcade and dexa­meth­a­sone im­proves pro­gres­sion free sur­vival by four months versus Velcade and dexa­meth­a­sone alone.

This im­prove­ment is likely to be enough for Novartis, the com­pany devel­op­ing panobinostat, to move for­ward with plans to submit an appli­ca­tion to the U.S. and European regu­la­tory author­i­ties later this year to have the drug approved as a new treat­ment for multiple myeloma.

Daratumumab & SAR650984

There also will be several pre­sen­ta­tions during the ASCO meeting featuring results of trials investigating daratumumab and SAR650984.  Both of these poten­tial new myeloma treat­ments belong to the class of drugs known as mono­clonal anti­bodies, and both work by targeting a protein known as CD38 that is fre­quently found on the surface of myeloma cells.

In the case of dara­tu­mu­mab, updated results will be pre­sented for two trials.  One is a Phase 1/2 trial in­ves­ti­gating the safety and efficacy of dara­tu­mu­mab as a single agent in re­lapsed myeloma patients, which will be discussed Dr. Henk Lokhorst from UMC Utrecht in the Netherlands in an oral pre­sen­ta­tion (abstract).  The other is a Phase 1/2 trial investigating the com­bi­na­tion of dara­tu­mu­mab, Revlimid (lena­lido­mide), and dexa­meth­a­sone as a treat­ment for re­lapsed myeloma patients.  Results of this trial will be covered in a re­search poster (abstract).

The updated results from both trials con­tinue to show that dara­tu­mu­mab has sub­stan­tial anti-myeloma activity.

Development of SAR650984 as an anti-myeloma agent has lagged that of dara­tu­mu­mab, but Sanofi, the com­pany that hopes to bring SAR650984 to mar­ket, is work­ing hard to close the gap.

Updated results of a Phase 1 trial testing SAR650984 in heavily pre­treated myeloma patients will be pre­sented during a poster session (abstract).  In addi­tion, the first results of a Phase 1b trial testing the com­bi­na­tion of SAR650984, Revlimid, and dexa­meth­a­sone in re­lapsed myeloma will be pre­sented by Dr. Thomas Martin from the University of California - San Francisco during the June 2 oral pre­sen­ta­tion session (abstract).

Both sets of results in­di­cate that SAR650984, like dara­tu­mu­mab, is highly active against multiple myeloma.

Revlimid & Thalidomide

The second set of results to be pre­sented at the oral pre­sen­ta­tion session on June 2 will be for a U.S. Phase 3 trial known as E1A06.  It in­volve­s more than 300 newly diag­nosed multiple myeloma patients.  Par­tic­i­pants in the trial were treated with either melphalan (Alkeran), prednisone, and Revlimid (MPR) or mel­phalan, pred­ni­sone, and thalidomide (Thalomid) (MPT) (abstract).

The E1A06 trial has been ongoing for five years, but the pre­sen­ta­tion at ASCO – which will be given by Dr. Keith Stewart of the Mayo Clinic – will be the first detailed look at its results.

The results con­tain a surprise or two.  Although Revlimid is often con­sidered to be a more effective drug than thalido­mide, re­sponse­ rates, pro­gres­sion-free sur­vival rates, and three-year over­all sur­vival rates for the MPR and MPT regi­mens are nearly identical in the E1A06 trial.  Indeed, for some of the metrics just men­tioned, the thalido­mide-con­tain­ing regi­men (MPT) posts numbers that are slightly better than the Revlimid-containing regi­men (MPR).

What will not be a surprise is that the MPT regi­men tended to be less tolerable than MPR among the pa­tients in the E1A06 trial.  There were more serious side effects observed in patients on the MPT regi­men, and measures of patient quality of life also were lower in the patients who re­ceived the thalido­mide-containing regi­men.

The pre­sen­ta­tion of the E1A06 trial results is likely to spark interest in the results of a large U.K. Phase 3 trial, which will be pre­sented during a poster session on Friday May 30 (abstract).  The so-called Myeloma XI trial thus far in­cludes nearly 2,000 newly diag­nosed multiple myeloma patients.  Par­tic­i­pants in the trial re­ceive initial treat­ment with either cyclophosphamide (Cytoxan), Revlimid, and dexa­meth­a­sone (CRD), or cyclo­phos­pha­mide, thalido­mide, and dexa­meth­a­sone (CTD).

The abstract for the poster in­di­cates that patients in the trial who have re­ceived the Revlimid-containing regi­men (CRD) have had deeper re­sponse­s than patients who have re­ceived the thalido­mide-containing regi­men (CTD).  Overall re­sponse­ rates for the two regi­mens, how­ever, were similar, and the abstract does not in­clude any data on the rates of pro­gres­sion-free or over­all sur­vival for the two regi­mens.

Continuous Therapy vs. Fixed Duration Of Therapy

A key pre­sen­ta­tion during last De­cem­ber’s American Society of Hematology annual meeting looked at the issue of long-term con­tin­uous ther­apy for newly diag­nosed multiple myeloma patients.

The pre­sen­ta­tion summarized initial results of the so-called FIRST trial.  It is com­par­ing three treat­ment regi­mens: con­tin­uous treat­ment with Revlimid and dexa­meth­a­sone (Rd) until pro­gres­sion; treat­ment with Rd for a fixed period of time; and treat­ment with mel­phalan, pred­ni­sone, and thalido­mide (MPT) for a fixed period of time.

The results pre­sented in De­cem­ber showed that con­tin­uous Rd ther­apy im­proved re­sponse­ rates and measures of sur­vival versus the alter­na­tive fixed-duration-of-therapy regi­mens (see related Beacon news).

At the Monday, June 2, myeloma oral pre­sen­ta­tion session at this year’s ASCO meeting, Dr. Antonio Palumbo of the University of Torino will present results of a study that further in­ves­ti­gates the poten­tial benefit of con­tin­uous ther­apy versus fixed duration of ther­apy (abstract).  The study makes use of data from two Italian trials involving newly diag­nosed multiple myeloma patients.

In both of the trials, there were two groups of patients – one that re­ceived con­tin­uous ther­apy, and one that re­ceived treat­ment for a fixed duration of time.  One trial in­volve­d Velcade-based treat­ment regi­mens, while the other in­volve­d Revlimid-based regi­mens.

Based on their analyses of the trial results, Dr. Palumbo and his colleagues conclude that, as was the case in the results for the FIRST trial, con­tin­uous ther­apy is more ad­van­tageous than treat­ment for a fixed duration of time.

The analysis that leads to this conclusion, how­ever, is less direct than was the case for the FIRST trial. Thus, it will be in­ter­est­ing to see how the study results are re­ceived during Dr. Palumbo’s pre­sen­ta­tion at the meeting.

Smoldering Myeloma

There will be four separate poster pre­sen­ta­tions at the ASCO meeting that seek to more precisely de­ter­mine which patients with smoldering myeloma are especially likely to progress to active (symptomatic) multiple myeloma.   Such patients are often described as having “high-risk”, or “ultra high-risk,” smol­der­ing myeloma.

Interest in the definition of high-risk smol­der­ing myeloma has grown due to an im­por­tant study that was pub­lished last year.  The study found that active treat­ment of high-risk smol­der­ing myeloma may be superior to the traditional “watch and wait” ap­proach to the dis­ease (see related Beacon news).

One of the four ASCO abstracts uses chromosomal ab­nor­mal­i­ties and free light chain measures to identify high-risk smol­der­ing myeloma patients (abstract).  A second study uses gene ex­pres­sion profiling (ab­stract).  A third links risk of pro­gres­sion to char­ac­ter­istics of a patient’s natural killer cells (large granular lym­pho­cytes) (abstract).  The fourth and final study uses a more traditional ap­proach, linking bone mar­row plasma cell per­cent­ages, free light chain ratios, and blood albumin levels to the risk of pro­gres­sion to active myeloma (abstract).

Other Potential New Treatments & Treatment Regimens

Updated results of a Phase 1/2 trial testing TH-302 and dexa­meth­a­sone in heavily pre­treated myeloma patients will be pre­sented during a poster session on Friday, May 30, at the ASCO meeting  (abstract).  The cur­rently avail­able results in­di­cate that TH-302 has anti-myeloma activity, but the level of this activity seems somewhat limited.

Also on Friday, a poster will be pre­sented summarizing initial results from a Phase 1 trial of a four-drug regi­men for re­lapsed myeloma.  The regi­men in­cludes Kyprolis (car­filz­o­mib), Revlimid, Zolinza (vorinostat), and dexa­meth­a­sone – a regi­men that trial in­ves­ti­ga­tors have labeled “QUAD” (abstract).   The regi­men appears to be effective, but it is unclear whether physicians will find it suf­fi­ciently effective to justify the side effects asso­ci­ated with a four-drug regi­men.

The meeting also will feature updated results for a trial testing the com­bi­na­tion of Pomalyst (poma­lido­mide, Imnovid), Velcade, and dexa­meth­a­sone in re­lapsed myeloma (abstract), and a separate trial testing weekly dosing of Kyprolis in com­bi­na­tion with dexa­meth­a­sone, also for re­lapsed myeloma (abstract).

Finally, there will be a poster pre­sen­ta­tion with results of a Phase 3 trial that is com­par­ing two dif­fer­en­t high-dose chemo­ther­apy regi­mens for use during au­tol­o­gous (own) stem cell trans­plan­ta­tion in myeloma pa­tients (abstract).   One group of patients in the study re­ceived a com­bi­na­tion of busulfan (Busulfex) and mel­phalan, spread out over several days, as their high-dose chemo­ther­apy prior to trans­plan­ta­tion, while the other group re­ceived a standard dose of mel­phalan as high-dose chemo­ther­apy.

The re­sponse­ rate to high-dose chemo­ther­apy was noticeably lower in the group of patients who re­ceived the busulfan-melphalan com­bi­na­tion, and the com­bi­na­tion also was asso­ci­ated with more side effects.  However, the com­bi­na­tion also led to somewhat higher one-year pro­gres­sion-free sur­vival.

For more in­for­ma­tion on ASCO’s 50^th Annual Meeting, in­clud­ing the final pre­sen­ta­tion schedule, abstracts, and in­for­ma­tion on attending, please see the American Society of Clinical Oncology meeting website.

Beacon coverage of myeloma-related re­search pre­sented at recent scientific meetings can be found at these links: ASH 2013 Meeting (including the ASH 2013 Multiple Myeloma Gateway), EHA 2013 Meeting, ASCO 2013 Meeting, and IMW 2013.