Physicians and researchers have started gathering for the 18th Congress of the European Hematology Association (EHA), which will take place in Stockholm this year. The first education and poster sessions of the meeting will take place tomorrow, Friday, June 14. Additional sessions of various kinds are scheduled for both days of the weekend, until the meeting ends early Sunday afternoon (European time).
The research presented at the meeting will cover all areas of hematology, which is the study of blood, blood-forming organs, and blood-related diseases, including multiple myeloma.
The EHA meeting is one of three annual scientific meetings where important myeloma-related research findings are often reported. The other two key annual conferences are the annual meetings of the American Society of Hematology (ASH) and the American Society of Clinical Oncology (ASCO).
This article summarizes some of the key myeloma-related findings that are expected to be presented at EHA during oral sessions on Saturday and Sunday. The findings discussed in the article are based on information currently available in the presentation abstracts.
These abstracts, it should be noted, often contain preliminary results which are further updated at the actual meeting. This article will therefore be revised from time to time as newer data become available during and after the meeting.
At the EHA and other scientific meetings, oral presentations are usually given for research that is considered to be particularly important, either because the subject itself is important, or because the results are based on substantial amounts of evidence (for example, a sizable clinical trial).
Additional research findings are presented at meetings in the form of poster research summaries. Such findings are made available during specific “poster sessions,” when researchers display summaries of their studies on posters in an 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.
Many of the key myeloma-related presentations at the EHA meeting will be similar to presentations given at the recently completed 2013 ASCO meeting, and others will provide updated results from studies discussed at the 2012 ASH meeting last December.
In this article, however, the key EHA presentations are covered in approximate order of importance, regardless of whether or not they are similar to, or updates to, presentations at the most recent ASCO and ASH meetings.
Daratumumab For Relapsed And Refractory Myeloma
During an afternoon oral presentation session on Saturday, Dr. Henk Lokhorst from University Medical Center in Utrecht, Netherlands will report results from the Phase 1 portion of a Phase 1/2 study of daratumumab in relapsed and refractory multiple myeloma patients (abstract). Dr. Lokhorst also presented these results at ASCO earlier this month (see related Beacon news; presentation [pdf] courtesy of Dr. Lokhorst). The results showed that 42 percent of patients who received at least 4 mg/kg of daratumumab responded; all of these responses were partial responses. The median progression-free survival for this subset of patients has not yet been reached after a median follow-up of 18.4 weeks. The most common mild to severe side effects were infusion-related.
Kyprolis Plus Revlimid And Dexamethasone For Relapsed / Refractory Myeloma
During the same Saturday session, Dr. Ruben Niesvizky from the Weill Cornell Medical College in New York City will present the final results of a Phase 1/2 study of Kyprolis (carfilzomib) plus Revlimid (lenalidomide) and low-dose dexamethasone (Decadron), commonly abbreviated as CRd, in patients with relapsed and refractory multiple myeloma (abstract). These results were also shown at ASCO, during a poster session, earlier this month (see related Beacon news; poster [PDF] courtesy of Dr. Michael Wang). The final results show that at a median follow-up time of 24.4 months, the overall response rate was 69 percent, with 5 percent of patients achieving a complete response, 36 percent a very good partial response, and 29 percent a partial response. The median progression-free survival was 11.8 months. The median overall survival was not reported. The most common side effects of any severity included fatigue (66 percent), diarrhea (56 percent), and low white blood cell counts (45 percent).
Pomalyst Plus Low-Dose Dexamethasone Versus High-Dose Dexamethasone Alone For Relapsed / Refractory Myeloma
On Sunday, Dr. Jesús San-Miguel from the University Hospital in Salamanca, Spain, will present updated results from a Phase 3 study comparing the efficacy and safety of Pomalyst (pomalidomide) in combination with low-dose dexamethasone (Decadron) versus treatment with only high-dose dexamethasone for heavily pretreated myeloma patients (abstract). Dr. Katja Weisel of the University Hospital in Tübingen, Germany, also presented results from this study earlier this month at ASCO (see related Beacon news; presentation [pdf] courtesy of Dr. Weisel).
The study results show that after a median follow-up of 10 months, Pomalyst plus low-dose dexamethasone had superior response rates and survival compared to high-dose dexamethasone alone. In particular, the overall response rates were 31 percent and 10 percent, respectively. In addition, median progression-free survival times were 4 months and 1.9 months, respectively, and median overall survival times were 12.7 months and 8.1 months, respectively. Severe low white blood cell counts were more common with Pomalyst treatment (42 percent versus 15 percent, respectively). Dr. San-Miguel will also report that the Pomalyst combination significantly improves quality of life.
Kyprolis Plus Cyclophosphamide And Dexamethasone For Older Newly Diagnosed Myeloma
During Saturday’s oral presentation session, Dr. Sara Bringhen from the University of Torino in Italy will discuss updated results from a Phase 1 study of Kyprolis, cyclophosphamide (Cytoxan), and dexamethasone in older newly diagnosed myeloma patients who were not eligible for stem cell transplantation (abstract). Earlier results from this study were presented at the ASH annual meeting last December (see related Beacon news). The updated results show that all study participants responded to therapy, with 23 percent achieving a stringent complete response, 30 percent a complete or near complete response, 24 percent a very good partial response, and 23 percent a partial response. The one-year progression-free survival rate was 88 percent, and the one-year overall survival rate was 87 percent. The most common severe side effects included low white blood cell counts (15 percent), low red blood cell counts (12 percent), infection (10 percent), heart-related issues (5 percent), and low platelet counts (5 percent).
ARRY-520 Plus Kyprolis For Relapsed And Refractory Myeloma
Also during Saturday’s session, Dr. Jatin Shah from the MD Anderson Cancer Center in Houston will present updated results of a Phase 1 study of the investigational drug ARRY-520 in combination with Kyprolis in relapsed and refractory myeloma patients (abstract). ARRY-520, which is being developed by Array BioPharma (NASDAQ: ARRY), inhibits kinesin spindle protein, which plays an important role in actively dividing cells. Earlier results from this study were presented in a poster at the ASH annual meeting in December 2012 (see related Beacon news). At the time, nine patients had been enrolled in the study with a median age of 67 years. Among those, 22 percent responded to therapy, with 11 percent achieving a complete response and 11 percent a partial response. Since then, a total of 17 patients with a median age of 71 years have been enrolled. The maximum tolerated dose has not been established yet. The most common severe side effects include pneumonia (24 percent), high calcium levels (12 percent), kidney failure (12 percent), and lethargy (12 percent).
Safety Of Revlimid Plus Cyclophosphamide And Dexamethasone For Newly Diagnosed Myeloma
On Sunday, Dr. Annamaria Brioli from the Institute of Cancer Research in London will present updated safety results for the Revlimid, cyclophosphamide, dexamethasone (RCD) arm of a Phase 3 trial comparing RCD to cyclophosphamide, thalidomide (Thalomid), and dexamethasone (abstract). So far, 1,882 patients have been recruited to the trial, half of whom are receiving treatment with RCD. Patients have received a median of five treatment cycles thus far. The most common side effects related to RCD treatment have included low white blood cell counts (25 percent), low red blood cell counts (13 percent), and low platelet counts (8 percent). Less than 1 percent of patients experienced peripheral neuropathy (pain, tingling, and loss of sensation in the extremities), which is frequently associated with thalidomide and Velcade therapy. Overall, 62 percent of patients required dose modifications on RCD. However, only 6 percent of patients have discontinued treatment due to side effects.
Subcutaneous Velcade Combinations
Also on Sunday, Dr. Alessandra Larocca from the University of Torino in Italy will present results from a Phase 2 trial investigating three different combination treatments of subcutaneous Velcade in elderly, newly diagnosed multiple myeloma patients (abstract). The study included 152 newly diagnosed patients with a median age of 77 years. Patients received treatment with subcutaneous Velcade plus prednisone (VP); or subcutaneous Velcade, cyclophosphamide, and prednisone (VCP); or subcutaneous Velcade, melphalan, and prednisone (VMP). Overall, 66 percent of patients were categorized as frail (78 percent in the VP treatment group, 57 percent in the VCP group, and 62 percent in the VMP group).
All three regimens were active in older myeloma patients, with overall response rates of 60 percent for VP, 60 percent for VCP, and 70 percent for VMP. Of the frail patients, 60 percent responded to VP, 52 percent to VCP, and 77 percent to VMP.
Overall, 31 percent of patients in the VP group, 41 percent in the VCP group, and 42 percent in the VMP group experienced at least one severe side effect. However, the rate of severe blood-related side effects was low (less than 10 percent in all groups). The rate of severe side effects was higher in frail patients (30 percent in the VP group, 52 percent in the VCP group, and 48 percent in the VMP group).
Due to side effects, 14 percent of patients in the VP group, 16 percent in the VCP group, and 22 percent in the VMP group discontinued treatment. The discontinuation rate due to side effects was also slightly higher in frail patients (15 percent in the VP, 21 percent in the VCP, and 23 percent in the VMP group).
CC-292 Plus Kyprolis Prevents Bone Degradation
Dr. Homare Eda from the Harvard Medical School will present on Saturday results from a preclinical study of the effect CC-292 plus Kyprolis has on bone degradation (abstract). CC-292, which is being developed by Celgene (NASDAQ: CELG), is an oral drug that inhibits a protein called Bruton’s tyrosine kinase that plays an important role in the growth of B-cells and osteoclasts, cells that break down bone. The results show that CC-292 blocks osteoclast function. They also show that CC-292 and Kyprolis work synergistically to block osteoclast function.
Tools For Determining Prognosis
Later on Saturday, Martin Van Vliet of Skyline Diagnostics will present the results of a retrospective analysis that investigated whether the gene expression profiling (GEP) and FISH testing can be used for risk stratification and prognosis determination in multiple myeloma (abstract). GEP simultaneously measures the activity of thousands of genes in a patient’s multiple myeloma cells, while FISH testing detects chromosomal abnormalities. The study results indicate that gene expression profiling is better able to identify high-risk patients and predict overall survival than chromosomal abnormalities identified by FISH.
Secondary Cancers
On Sunday, Dr. Sara Bringhen from the University of Torino in Italy will discuss the results from a meta-analysis investigating the relationship between treatment with Revlimid and the likelihood of developing a secondary cancer (abstract). Dr. Antonio Palumbo from the University of Torino presented results from the same study at ASCO earlier this month (see related Beacon news; presentation [pdf] courtesy of Dr. Palumbo). The analysis was based on data from 6,383 myeloma patients with a median age of 69 years who participated in a number of different randomized clinical trials. Many, but not all, of the patients had received treatment with Revlimid.
The study results show that after a median follow-up of 30 months, 6.6 percent of patients developed secondary cancers. This includes 2.9 percent who developed blood cancers and 3.6 percent who developed solid tumors. The rate of blood cancers was significantly higher in patients treated with Revlimid. However, the investigators found that this increased risk was limited to patients treated with Revlimid in combination with, or soon after treatment with, melphalan (Alkeran).
Velcade Before Stem Cell Transplantation
Also on Sunday, Dr. Michele Cavo from the Bologna University School of Medicine in Italy will present the results of a meta-analysis investigating the impact of Velcade-based initial therapy on outcomes after stem cell transplantation, including in patients with the high-risk chromosomal abnormalities t(4;14) and/or del(17p) (abstract).
The analysis is based on data from 2,169 myeloma patients who participated in four randomized clinical trials. Three Velcade-based combination regimens were tested in those trials: Velcade and dexamethasone; Velcade, thalidomide and dexamethasone; and Velcade, doxorubicin (Adriamycin), and dexamethasone.
In addition, two combination regimens not including Velcade were investigated: the older chemotherapy-based regimen known as VAD, and thalidomide combined with dexamethasone.
Across all patients, the results showed that Velcade-based initial therapy led to a higher rate of complete responses before stem cell transplantation compared to non-Velcade based regimens (15 percent versus 4 percent). The researchers also observed a trend to higher response rates for Velcade-based regimens in patients with high-risk chromosomal abnormalities (18 percent versus 0 percent).
At a median follow-up of 37 months, median progression-free survival was significantly longer for patients who received Velcade-based initial therapy (41.5 months versus 33 months). The researchers found that extended progression-free and overall survival across all patients, as well as those with high-risk chromosomal abnormalities, was particularly associated with three factors: achievement of a complete response after initial therapy, a double transplant, and Velcade-based initial therapy.
Patients who carried both t(4;14) and del(17p) had the worst treatment outcomes and, according to the researchers, would benefit the most from novel agent-based double stem cell transplantation.
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For more information on the 18th EHA Congress, including the final presentation schedule, abstracts, and information on attending, please see the Congress of the European Hematology Association website.
Beacon coverage of myeloma-related research presented at recent scientific meetings can be found at these links: ASCO 2013 Meeting, IMW 2013, and ASH 2012 Meeting.
Note: Electronic copies of conference presentations and posters made available to the Beacon’s readers are for personal use only. Further transmission or publication of the files is not permitted, although hyperlinks to the files are permitted with attribution to the author and to The Beacon (for example, “courtesy of Dr. Jane Doe and The Myeloma Beacon.”)