This year’s International Myeloma Workshop (IMW) started in Paris yesterday morning and will continue through Friday.

Yesterday’s schedule included three sessions of oral presentations and a poster session in the afternoon.  The focus of the oral sessions was to present the current understanding of the biochemistry and molecular mechanisms related to multiple myeloma.

These talks were more technical than the ones that will be made later in the week, and their material will not likely have an immediate impact on how current multiple myeloma patients are treated.

In particular, yesterday’s sessions included one in the morning on molecular pathways and genetics, a second one in the early afternoon on plasma cell biology, and a third one late in the afternoon and early evening on bone disease and animal models.

Some of the highlights from Day 1 of the IMW are summarized in this article.

Molecular Pathways And Genetics

During the first presentation of this session, Dr. Carol Croce of Ohio State spoke about microRNAs in myeloma and other cancers.

MicroRNA is a special kind of RNA that, unlike most RNA, is not directly involved in the production of proteins in the body.  Instead, microRNA is very small RNA that helps control the process of producing proteins from genes.  Humans have about 1,000 different types of microRNA.

Based on his research, Dr. Croce believes that “microRNA is involved in all human cancer” and that it plays a key role in why mutations of the p53 gene are so important in multiple myeloma.

Additionally, Dr. Croce believes that one day multiple myeloma patients may be classified based on the kinds of microRNA involved in their disease and that drugs containing microRNA or that affect the production of microRNA may be powerful new treatment options for myeloma.

Nutlin and its various derivatives appear to affect microRNA production and the progression of myeloma and may potentially be used to treat myeloma in the future.

The second presentation during this session was by Dr. Rafael Fonseca of the Mayo Clinic.  He spoke about the classification of myeloma and subtypes of the disease.

According to Dr. Fonseca, myeloma researchers often begin by classifying patients into one of two broad categories.  Patients either have chromosomal mutations resulting in more than the normal two copies of a chromosome (“hyperdiploidy”) or they have a translocation of a region of one chromosome to another, for example t(14;16).  Each of these broad categories of patients accounts for about half of all myeloma patients, but some patients can have translocations and hyperdiploidy.

From here, the best way to further classify patients is still debated.  However, it is clear that there are many different subtypes of myeloma patients.  Dr. Fonseca said that he believes there are “many, many, many multiple myelomas.”

In general, however, Dr. Fonseca said that younger multiple myeloma patients typically have higher risk chromosomal abnormalities, not as much bone disease, and IgA lambda proteins.  Older patients, in contrast, are not as inclined to have high-risk chromosomal abnormalities, but they typically have more bone disease and IgA kappa proteins.

Additionally, myeloma patients typically progress from having intramedullary disease (confined to the bone marrow) to having extramedullary disease (extending into other parts of the body).  Likewise, mutation of the p53 gene is typically a good measure of disease progression.

He also briefly mentioned the different analytical methods available to physicians for categorizing multiple myeloma patients.  One method that is very common is FISH analysis.  However, Dr. Fonseca believes that gene expression profiling offers even richer data for classifying patients.

The final presentation of the morning session was by Dr. Stéphane Minvielle of the University of Nantes, France.  He spoke on the genetic progression of multiple myeloma.

Dr. Minvielle noted that, until recently, it was very challenging to trace how a single multiple myeloma patient’s chromosomal abnormalities evolve over time.  With newer and more advanced tools, this has become easier to do.

Although Dr. Minvielle and his colleagues have begun tracking the evolution of chromosomal abnormalities in a number of myeloma patients, the evolution appears to be relatively unique for each patient.

Interestingly, Dr. Minvielle’s study showed that patients taking Velcade (bortezomib) plus dexamethasone (Decadron) were more likely to have a chromosomal abnormality that persisted through treatment, as compared to patients treated with an older and less commonly used regimen of vincristine, doxorubicin (Adriamycin), and dexamethasone.

Bone Disease

The afternoon session consisted of several short presentations on the current understanding of bone disease in myeloma.

Bone disease is a common complication associated with multiple myeloma.  Myeloma cells disrupt the normal cycle of bone formation and destruction, resulting in weakened bones that easily break.

The first talk of the session was given by Dr. David Roodman from the University of Pittsburgh.

Dr. Roodman stated that 70 percent of myeloma patients have bone pain, 20 percent have a fracture at diagnosis, and 60 percent sustain a fracture over the course of their disease.  In addition to the pain and suffering that bone disease can cause, fractures also result in a 20 percent increase in mortality for myeloma patients.

He also discussed a number of new approaches that researchers are pursuing in the treatment of myeloma bone disease, including Xgeva (denosumab), as compared to standard bisphosphonate therapy using Zometa (zoledronic acid) or Aredia (pamidronate).

Next, Dr. Shmuel Yaccoby of the University of Arkansas for Medical Sciences spoke about bone formation and tumor growth in myeloma.

He described how he and his colleagues have had success treating myeloma bone disease with daily subcutaneous injections of parathyroid hormone.  Not only does it help with bone disease, but it seems to have anti-myeloma activity as well.

Then Dr. Nicola Guiliani from the University of Parma, Italy spoke about the effect of novel agents on bone microenvironment cells.

He explained that one reason the new myeloma drugs such as Velcade and Revlimid (lenalidomide) are so effective against multiple myeloma is that they do more than just attack the malignant myeloma cells in patients’ bone marrow.  They also act against myeloma bone disease.  All of the novel agents appear to reduce the number of cells that break down bone, and Velcade appears to also increase the number of cells that rebuild bone.

The final talk in the session was given by Dr. Karin Vanderkerken of the Vrije Universiteit Brussel, Belgium.  She spoke about epigenetic changes of myeloma cells.

“Epigenetic” changes in a person’s protein production are changes that are abnormal, but which are not due to any mutations in the patient’s DNA.  These changes can potentially be reversed using one or more epigenetic drugs.

Dr. Vanderkerken discussed how two existing epigenetic drugs, Vidaza (azacitidine) and Dacogen (decitabine), have been shown in pre-clinical studies to have anti-myeloma activity.  In addition, two epigenetic drugs under development, JNJ-26481585 and panobinostat, also have been shown to be effective against myeloma cells and myeloma bone disease in pre-clinical studies, especially in combination with Velcade and Dacogen, respectively.

For more detailed summaries of the day's sessions, see The Myeloma Beacon’s extensive Day 1 coverage in the Beacon Forums.  For links to abstracts of some of the presentations given during the day, see the IMW programme. The Myeloma Beacon will be publishing regular “as it happens” updates from Day 2 of the IMW in this thread in the Beacon’s myeloma forums.  Similar updates will also be provided for Day 3 and Day 4.  News from each day will also be summarized in daily updates like this one.