Today is the last day of this year’s American Society of Clinical Oncology (ASCO) annual meeting, which is being held in Chicago. However, the multiple myeloma-related presentations at the meeting concluded yesterday.

A poster session yesterday afternoon featured research on a wide variety of myeloma-related topics, ranging from new treatments being developed for myeloma, to currently used regimens, to second cancers, to precursor myeloma diseases, and much more.

This article summarizes research from that session related to prognostic factors, precursor myeloma diseases, peripheral neuropathy, osteo­necrosis of the jaw, and second cancers.

A summary of the results from posters about treatments under development was published yesterday (see related Beacon news); a summary of posters about currently used treatments was published earlier today (see related Beacon news).

Prognostic Factors

The results reported in one of yesterday's posters were from a retrospective analysis by researchers at the MD Anderson Cancer Center in Houston.

The analysis investigated whether the percentage of plasma cells in a myeloma patient's bone marrow prior to stem cell transplantation has an impact on treatment outcomes (abstract).

The study drew on data from 1,489 myeloma patients who underwent stem cell transplantation between August 1998 and December 2010 at MD Anderson. Patients were divided into two groups based on the amount of plasma cells in the bone marrow:  low (less than 10 percent of plasma cells) and high (more than 10 percent of plasma cells).

The researchers found that lower plasma cell levels in the bone marrow were associated with better treatment outcomes.  Patients with less than 10 percent of plasma cells achieved deeper responses and longer progression-free and overall survival times than patients with more than 10 percent of plasma cells in the bone marrow.

The differences in progression-free and overall survival times between the two groups persisted even into the period of time when so-called "novel" myeloma treatments -- thalidomide (Thalomid), Velcade (bortezomib), and Revlimid (lenalidomide) -- began to be used more frequently as initial therapy for newly diagnosed myeloma patients.

MGUS And Smoldering Myeloma

Yesterday's poster session included a couple of posters on the myeloma precursor diseases monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma.

One poster included preliminary results from an ongoing study investigating the role of auto-immune disorders in disease progression (abstract).  Auto-immune disorders such as rheumatoid arthritis and psoriasis develop when the immune system attacks the body's own healthy body tissue.

Of the 60 MGUS patients and 56 smoldering myeloma patients included in the study, 15 percent of MGUS patients and 12 percent of smoldering myeloma patients had pre-existing auto-immune disorders.

The researchers used certain plasma cell markers to determine whether patients were at high risk of progressing to symptomatic (active) multiple myeloma.  Higher levels of these markers generally mean a higher risk of progression.

The study authors found that smoldering myeloma patients with pre-existing auto-immune disorders had lower levels of the plasma cell markers than the other smoldering patients, suggesting that the patients with the pre-existing immune disorders were at a lower risk of progressing to active myeloma.

In MGUS patients, the plasma cell marker levels were similar among patients with and without pre-existing auto-immune disorders, meaning that the pre-existing auto-immune disorders are unlikely to affect the risk of progression in this patient population.

In another poster, researchers from the National Institutes of Health (NIH) compared the two models currently used to determine the risk of progression from smoldering multiple myeloma to symptomatic multiple myeloma (abstract).

One model, which was developed by Spanish myeloma experts, uses the fraction of abnormal plasma cells on flow cytometry to evaluate risk. The other model, developed by myeloma experts at the Mayo Clinic, uses fractions of bone marrow plasma cells and blood protein levels to determine risk.

The NIH researchers evaluated 70 smoldering myeloma patients using both models. They found that there were significant differences in the way the two models categorized the patients.

They researchers therefore advocate the introduction of risk stratification models that rely on molecular markers to predict disease progression.

Peripheral Neuropathy

Peripheral neuropathy is a common side effect of myeloma treatments such as Velcade and thalidomide.  It is characterized by pain, tingling, or loss of sensation in the extremities.

Velcade inhibits the activity of proteasomes, which are enzymes that break down important proteins in both healthy and cancerous cells.

One poster included in yesterday’s session showed results from a Japanese study that investigated if proteasome activity could be used to predict the occurrence of peripheral neuropathy in patients treated with Velcade.

The study included data from 21 myeloma patients who had been treated with Velcade. The researchers found that one hour after the Velcade administration, proteasome activity decreased below pretreatment levels but generally recovered to pretreatment levels by the end of the first treatment course.

However, of the patients whose proteasome activity did not recover to pretreatment levels by the end of the first treatment course, 42 percent showed signs of peripheral neuropathy during the second or third course of treatment.

The researchers conclude that patients whose proteasome activity does not recover to pretreatment levels by the end of the first treatment course may be at an increased risk of developing peripheral neuropathy.

The issue of peripheral neuropathy also was addressed during an oral presentation at today's sessions of the ASCO meeting.  It reported results from a Phase 3 clinical trial studying whether Cymbalta (duloxetine) improves chemotherapy-induced peripheral neuropathy (abstract).

Patients included in this study were not specifically myeloma patients.  Indeed, almost all the patients in the study had other kinds of cancer, and the patients were treated with drugs not commonly used in the treatment of myeloma.  The results of the study therefore need to be interpreted cautiously when considering their relevance to treating peripheral neuropathy in myeloma patients.

The study results show that patients treated with Cymbalta were more likely to report a decrease in pain (59 percent) than those who received a placebo (39 percent).  In addition, Cymbalta's efficacy in reducing pain was similar regardless of which chemotherapy patients received.

The most common side effect associated with Cymbalta was fatigue.

Osteonecrosis Of The Jaw

Osteonecrosis of the jaw is a condition associated with a loss of blood supply to the jaw, causing the jawbone tissue to die. It can occur in a small fraction of multiple myeloma patients during bisphosphonate treatment. In multiple myeloma, bisphosphonates are commonly given to decrease bone pain and reduce the development of bone disease associated with myeloma.

Since not all myeloma patients develop osteonecrosis of the jaw when receiving bisphosphonate treatment, other factors may play a role in the development of the complication.

One of the posters included in yesterday’s session summarized results from a retrospective study that sought to identify risk factors for the development of osteonecrosis of the jaw (abstract).

The analysis was based on data from 231 myeloma patients treated at Northwestern University between January 1998 and September 2010.

The researchers found that the achievement of a partial or complete response and use of the combination treatment dexamethasone (Decadron), thalidomide, cisplatin, doxorubicin (Adriamycin), cyclophosphamide (Cytoxan), and etoposide (DT-PACE) were associated with an increased risk of developing osteonecrosis of the jaw. They recommend that patients treated with DT-PACE be closely assessed for symptoms of osteonecrosis of the jaw.

Second Cancers

An increased rate of second cancers has been observed in multiple myeloma patients who receive Revlimid maintenance therapy (see related Beacon news).

However, according to researchers at the Penn State Hershey Cancer Institute, the rate of second cancers among the overall myeloma population is unknown.

Yesterday’s session included a poster that summarized results from a retrospective study that analyzed the rate of second cancers in all myeloma patients treated at Hershey Medical Center between 2006 and 2010 (abstract).

Of the 320 myeloma patients included in the study, 13 percent were found to have more than one type of cancer.

However, in 72 percent of these cases where myeloma patients had more than one cancer, myeloma itself was the second cancer.

Overall, 75 percent of the patients in the study had received treatment with Revlimid. In the patients who developed a second cancer after their myeloma diagnosis, 64 percent had received treatment with Revlimid.

Additional coverage of key research results from the ASCO 2012 annual meeting will continue throughout the rest of the week in individual, topic-specific news articles.

For all Beacon articles related to this year’s ASCO meeting, see The Beacon’s full ASCO 2012 coverage.