Dr. Sagar Lonial, associate professor at the Winship Cancer Institute of Emory University and trained bone marrow physician, recently commented on two studies in the journal Blood that focused on high-risk multiple myeloma.

Lonial, an ad hoc article reviewer for Blood, Cancer Research, and other journals, has a particular interest in molecular therapies for lymphoma and myeloma. His recent research focuses on combinations of novel drugs that could be used to treat the two diseases.

In his article, titled “Risky Business in Myeloma,” Lonial discusses, in part, the impact of high-risk chromosomal abnormalities on myeloma patient response to a combined Revlimid ^[1] (lenalidomide)-dexamethasone ^[2] (Decadron) therapy.

Chromosomes carry genetic information in the form of DNA. Chromosomal abnormalities occur when DNA is deleted, duplicated, or even translocated from one chromosome to another.

Certain chromosomal abnormalities have been detected in high-risk myeloma patients. These include a deletion of part of the thirteenth chromosome, a translocation between the fourth and fourteenth chromosomes, and the deletion of a portion of the seventeenth chromosome.

Lonial acknowledges the importance of studies that examine such high-risk abnormalities. “Given the move toward individualized therapy based on risk, these studies are critically important in helping to identify the relative utility of Revlimid among a group of patients whose outcomes are historically quite poor,” said Lonial.

Lonial additionally says interpretation of the studies leads clinicians to both good and bad news.

The bad news, he explains, is that risk matters. Recent studies show that high-risk myeloma patients have a significantly shorter duration of remission than other patients. Though certain treatments are more effective than others (for example, one study showed that a combined Revlimid-dexamethasone therapy was more successful than just dexamethasone), high-risk patients still experience a shorter response duration than standard-risk patients.

Lonial cites one particular treatment, a combined Velcade ^[3] (bortezomib)-melphalan ^[4] (Alkeran) therapy, that has been shown to overcome high-risk features, but he says that important data on progression-free survival and overall survival is still pending.

The good news that can be reached from interpreting the studies is that risk may matter less. Lonial explains that though deletions on chromosome 13, translocations between chromosomes 4 and 14, and deletions on chromosome 17 are all grouped together as high-risk, they do not signify equally poor prognosis. The deletion on chromosome 17 has been shown to be more high-risk than either of the other two abnormalities.

Lonial also analyzes what risk means to myeloma patients. He acknowledges that it will be hard to find single drug agents that will be successful at combating high-risk myeloma. Rather, combination therapies with maintenance will be the minimum if there will be improvements in progression-free survival and overall survival for this group.

He ends his statement by saying both trials make it clear that response rate alone is not enough to judge whether a treatment is truly successful in high-risk patients. He says that further improvements for these individuals will require analysis of time to progression, complete remission duration, and overall survival.

For more information, please read Lonial’s comment ^[5] on the Blood Web site.