Researchers at the Mayo Clinic applied risk stratification in newly diagnosed myeloma patients receiving Revlimid ^[1] (lenalidomide) and dexamethasone ^[2] (Decadron) therapy. They found that progression-free survival was lower for high-risk patients compared with standard-risk patients.

Risk stratification examines the risk factors that lead to a reduced survival rate in patients, and it is a useful way of understanding why some treatments only work well for some patients. The scientists looked at 100 newly diagnosed multiple myeloma patients who had been given Revlimid-dexamethasone for the first treatment and examined them based on genetic abnormalities and a labeling index.

Of the 100 patients, 16 had high-risk multiple myeloma characterized by less than 46 chromosomes, which is known as hypodiploidy. Specifically, these patients exhibited partial deletion of chromosome 13, a deletion of tumor suppressor p53 on chromosome 17, and translocations from chromosomes four to 14 or 14 to 16. P53 is a gene that functions as a tumor suppressor, because it regulates the cell cycle.

The other characterization of high-risk multiple myeloma is a cytogenetic test: plasma cell labeling index (PCLI). PCLI measures the growth of plasma cells in the blood and is a diagnostic for new patients. Another cytogenetic test called fluorescent in-situ hybridization (FISH), checks for specific DNA sequences on chromosomes. However, not all patients in the study had this treatment done.

Of the 100 patients, 95 underwent a cytogenetic test. Those that did not were placed in the standard-risk category.

For the study, they looked at data of initial Revlimid-dexamethasone therapy from March 2004 to November 2007. All of the patients received Revlimid at 25 mg per day for 21 days during a four-week cycle in combination with a low-dose or high-dose of dexamethasone. They analyzed the data using the IMWG ^[3] uniform response criteria.

The median progression-free survival was 18.5 months for the high-risk group compared with 36.9 months for the standard-risk group. The overall response of high-risk patients and standard-risk patients was on par with previous studies.

Although the overall results indicate similar outcomes, it’s important to note the differences in this study and previous studies. This study had a small sample size, while a comparable Canadian study examined 159 relapsed multiple myeloma patients. Also, this study lacked uniform risk stratification in the sample. Some patients had three characteristics of high-risk multiple myeloma and others only had two.

Even with the differences, the overall results indicate that high-risk multiple myeloma patients do not respond as well to Revlimid-dexamethasone therapy. Risk stratification can be used to understand the implications of genetic differences and optimize treatments for high-risk and relapse patients.

For more information, see the article in the Blood ^[4] journal (article abstract viewable for free; full article available for a fee).