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). In total, 58 myeloma patients with a median age of 71 years have been in­cluded in the study. Currently, 96 per­cent of study par­tic­i­pants have responded to ther­apy, with 24 per­cent achieving a stringent com­plete response, 40 per­cent a com­plete or near com­plete response, 12 per­cent a very good partial response, and 20 per­cent a partial response. According to the updated results, the one-year pro­gres­sion-free survival rate was 86 per­cent, and the one-year over­all survival rate was 87 per­cent. The most common severe side effects in­cluded low white blood cell counts (17 per­cent), low red blood cell counts (11 per­cent), in­fec­tion (6 per­cent), heart-related issues (4 per­cent), res­pira­tory issues (4 per­cent), gastro­in­tes­ti­nal issues (4 per­cent),  low platelet counts (4 per­cent), and fatigue (4 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 (filanesib) in com­bi­na­tion with Kyprolis in re­lapsed and refractory myeloma patients (abstract; presentation [PDF] courtesy of Dr. Shah). 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, 2,110 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 in­fec­tions (40 per­cent), low blood cell counts (18 per­cent), and blood vessel-related com­pli­ca­tions (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, 64 per­cent of patients required dose modifications on RCD. However, only 8 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 older, newly diag­nosed multiple myeloma patients (abstract). The study in­cluded 152 newly diag­nosed patients with a median age of 78 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, 60 per­cent of patients were categorized as frail (69 per­cent in the VP treat­ment group, 53 per­cent in the VCP group, and 58 per­cent in the VMP group).

All three regi­mens were active in older myeloma patients, with over­all response rates  of 67 per­cent for VP, 63 per­cent for VCP, and 80 per­cent for VMP. The abstract states that among the frail patients, 60 per­cent responded to VP, 52 per­cent to VCP, and 77 per­cent to VMP.

After a median follow-up time of 17 months, pro­gres­sion-free survival and over­all survival were similar for all three treat­ment groups.  However, both types of survival appear to be somewhat shorter for VP com­pared to the other two regi­mens.

Progression-free survival and over­all survival were sig­nif­i­cantly higher, though, for fit older patients com­pared to frail older patients.

The abstract states that 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 (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).  Dr. Larocca stated, though, that mel­phalan seemed more toxic than cyclophosphamide.

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.”)