Latest Myeloma Research To Be Presented At The American Society Of Clinical Oncology Annual Meeting (ASCO 2014)
Published: May 15, 2014 1:01 pm
The American Society of Clinical Oncology will hold its 50th 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.
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.
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.
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 50th 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.
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