This year’s Congress of the European Hematology Association (EHA) is cur­rent­ly being held in Stockholm. It started earlier this week and will run through Sunday, June 16.

A substantial amount of myeloma-related research will be presented during the EHA meeting during both oral presentations and poster pre­sen­ta­tions.

This article summarizes some of the important myeloma-related findings that are expected to be presented during poster sessions today and to­mor­row. A previous article covered the key findings that will be pre­sented during oral pre­sen­ta­tions.

The studies covered in this article are primarily ones which have not been presented at pre­vi­ous scientific meetings.  The study findings summarized here are based on the cur­rently available presentation abstracts.

Such 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.

Ixazomib (MLN9708) Plus Revlimid And Dexamethasone In Older Patients

One of the posters presented today showed the results of a sub-analysis of data from a Phase 1/2 study of ixazomib (MLN9708) in com­bi­na­tion with Revlimid (lena­lido­mide) and dexamethasone (Decadron) in newly diagnosed multiple myeloma patients. The sub-analysis focuses on the efficacy of ixazomib in older patients (abstract).

Ixazomib is an orally-administered proteasome inhibitor, the same class of drugs to which Velcade (bortezo­mib) and Kyprolis (car­filz­o­mib) belong; it is being developed by Millennium Pharmaceuticals, the same com­pany that developed and markets Velcade.

Initial results of the entire study show that ixazomib may be highly effective in newly diagnosed patients (see related Beacon news).

The study included 65 patients of whom 52 per­cent were 65 years and older and 18 per­cent were 75 years and older.

Overall, 91 per­cent of patients aged 65 and older and 82 per­cent of patients aged 75 and older responded to the treat­ment, compared to 94 per­cent of patients under the age of 65.

According to the researchers, the rate of severe and life-threatening side effects was similar across the age groups.

MDX-1097 For Relapsed Kappa Myeloma

Tomorrow’s posters will include one that summarizes the results of a Phase 2a study of an anti­body, MDX-1097, for the treat­ment of re­lapsed myeloma that produces kappa light chains (abstract).

MDX-1097, which is being developed by the bio­technology com­pany Immune System Therapeutics, targets myeloma cells that produce kappa light chain proteins and triggers the immune system to kill the cancer cells.

The study included 19 patients who received eight weekly infusions of the anti­body; 26 per­cent of the par­tici­pants concurrently received Revlimid main­te­nance ther­apy.

Overall, 5 per­cent of patients achieved and maintained a very good partial response for a year, and 11 per­cent achieved a partial response.

MDX-1097 was well tolerated, with 21 per­cent of patients experiencing a serious side effect, such as a complete heart block, pneu­monia, low red blood cell counts, or inflammation of the pancreas, and 21 per­cent of patients experiencing mild to mod­er­ate infusion reactions.

ACY-1215 In Combination With Velcade or Revlimid

One of tomorrow’s posters will present two clinical trials involving ACY-1215 for the treat­ment of re­lapsed myeloma (abstract; poster [pdf] courtesy of Dr. Noopur Raje).  The first trial is studying ACY-1215 alone and in com­bi­na­tion with Velcade and dexa­meth­a­sone.  The second trial is studying ACY-1215 in com­bi­na­tion with Revlimid and dexa­meth­a­sone.

ACY-1215 is an oral histone deacetylase inhibitor, which means it works by interrupting cell division and causing cell death.  Other drugs in this class include Zolinza (vorinostat) and panobinostat.

At the time of the analysis, the first study included 28 re­lapsed and refractory myeloma patients with a median age of 66 years who had received a median of more than four prior lines of ther­apy.  Among the 15 patients who received only ACY-1215, 40 per­cent achieved stable disease.  Among the 13 patients who received ACY-1215 plus Velcade and dexa­meth­a­sone, 23 per­cent achieved a partial response.

The second study included 13 re­lapsed and refractory myeloma patients with a median age of 64 years who had received a median of three prior lines of ther­apy.  Among the 10 patients evaluated for response, 10 per­cent achieved a complete response, 20 per­cent a very good partial response, and 40 per­cent a partial response.

The most common severe side effects experienced while taking ASC-1215 alone were elevated creatinine levels (33 per­cent), fatigue (27 per­cent), elevated cal­cium levels (27 per­cent), and upper res­pira­tory in­fec­tions (27 per­cent).

Amifostine For The Prevention Of Peripheral Neuropathy

Another poster to be presented tomorrow will include results of a Chinese study that tested whether ami­fos­tine (Ethyol) can protect myeloma patients against periph­eral neu­rop­athy without affecting the efficacy of their treat­ment (abstract).  Peripheral neu­rop­athy is nerve damage that can cause pain, tingling, and numb­ness in the hands and feet.

Amifostine, which is approved to reduce certain side effects of chemotherapy and radiation, has pre­vi­ously been shown to prevent neu­rop­athy caused by certain types of chemotherapy.

The study included 47 newly diagnosed myeloma patients.  All of the participants were treated with Velcade, thalidomide (Thalomid), and dexa­meth­a­sone; half also received amifostine prior to each Velcade treat­ment.

The results show that amifostine did not affect the efficacy of the myeloma ther­apy; complete response rates were 35 per­cent for those who received amifostine and 38 per­cent for those who did not.

Overall, amifostine did not significantly reduce the rate of periph­eral neu­rop­athy (62 per­cent for those who received amisfostine versus 78 per­cent for those who did not); however, it did significantly lower the rate of severe periph­eral neu­rop­athy (8 per­cent versus 39 per­cent, respectively).

Secondary Cancers

Another of today’s posters summarized the first results of an analysis of secondary cancers in a large, on­go­ing British Phase 3 trial involving initial and main­te­nance ther­apy with Revlimid (abstract).

The trial compares the efficacy and safety of initial ther­apy with Revlimid, cyclophosphamide (Cytoxan), and dexa­meth­a­sone to initial ther­apy with thalido­mide, cyclophosphamide, and dexa­meth­a­sone. Patients can then receive further Velcade-based ther­apy if needed and a stem cell trans­plant if eligible.  Half of the patients will then receive Revlimid main­te­nance ther­apy, and half will not.

So far, 2,110 patients have been recruited to the trial; almost all have been begun induction ther­apy; 696 have entered the main­te­nance phase of the study.

At a median follow-up time of 1.3 years, the researchers report that the rate of secondary cancers has been very low; 14 cases of secondary cancers have been reported, of which 64 per­cent were observed in patients receiving initial ther­apy with thalido­mide.

However, the researchers point out that longer follow-up is needed to fully assess the risks.

Bone Biomarker CTX-1 For Predicting Myeloma Relapse

One of tomorrow’s posters will present results of a Irish study that indicate a bone bio­­marker known as CTX-1 can be used to predict progressive bone disease and myeloma relapse (abstract).

Multiple blood samples were taken over time from 27 patients with newly diagnosed myeloma, 30 myeloma patients in remission, 22 re­lapsed myeloma patients, and 27 healthy individuals; CTX-1 levels in each of these samples were measured.

The results show that newly diagnosed and re­lapsed patients have significantly higher CTX-1 levels than healthy individuals and myeloma patients in remission.  CTX-1 levels rose at least two-fold a median of three months prior to relapse.

The researchers state that CTX-1 testing is more cost effective and accessible than imaging and suggest that it should be used routinely.

Identification Of Very High-Risk Myeloma Patients

Another poster to be presented tomorrow will report results of an analysis that identified several charac­ter­istics that could be used to identify patients with very high-risk myeloma (abstract).

The study, which was carried out in Greece, included 246 myeloma patients; they had a median progres­sion-free survival of 26 months and a median over­all survival of 51 months; however, 5 per­cent of the patients died within two months of starting treat­ment.

The researchers found that 4 per­cent of the patients had Inter­na­tional Staging System stage 3 myeloma, high-risk chromosomal ab­nor­mal­i­ties, and high LDH levels and were at much higher risk of early pro­gres­sion (one year) and shorter survival (two years).

The researchers suggest that patients in this very high-risk group par­tic­i­pate in clinical trials to expand their available treat­ment options.

Effects Of Autoimmune Diseases On MGUS Survival

One of today’s posters summarized the results of a retrospective analysis that assessed the impact of autoimmune diseases on survival of people with monoclonal gammopathy of undetermined significance (MGUS) and people with multiple myeloma (abstract).

The analysis is based on Swedish data for 4,432 patients with MGUS, who were diagnosed between 1988 and 2006; 2,765 patients with multiple myeloma, who were diagnosed between 2000 and 2006 (before novel agents were approved to treat myeloma); and 28,119 healthy individuals.

The results show that a history of autoimmune diseases was linked to an increased risk of death in MGUS patients and in myeloma patients. However, the results also show that having an autoimmune disease has a bigger impact on the survival of healthy individuals than patients with MGUS or multiple myeloma.

The researchers suggest that under­lying con­di­tions, including autoimmune diseases, should be taken into account when managing MGUS and myeloma.

ABT-199

Another of today’s posters summarized results from a preclinical study that assessed the efficacy of the investigational drug ABT-199 in mice with multiple myeloma (abstract).

ABT-199, which is being developed by the bio­pharma­ceu­tical com­pany AbbVie, is a com­­pound that targets Bcl-2 and Bcl-2-related proteins, which regulate cell death.

The results show that the ABT-199 may be effective in myeloma cells with the chromosomal ab­nor­mal­ity t(11;14).

Two clinical trials studying ABT-199 are cur­rently recruiting myeloma patients.

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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.