Results of a recent study suggest that high-risk multiple myeloma patients who have chromosomal abnormalities known as trisomies have better survival outcomes than high-risk patients without them.

“Our findings allow us to further trim down the proportion of patients with truly high-risk disease, thus allowing us to concentrate on those patients and improve their outcome,” said Dr. Shaji Kumar of the Mayo Clinic in Rochester, Minnesota, and lead author of the study.

Based on their results, the researchers recommended a new and more specific method of classifying myeloma patients based on their disease risks by separating patients who have high-risk chromosomal abnormalities along with trisomies from patients who have only high-risk chromosomal abnormalities.

“Currently, we have patients who appear to do well despite being considered high-risk by current definitions, highlighting the lack of specificity with current systems,”  Dr. Kumar told The Beacon.

The researchers added that this new method may influence future treatment decisions by placing greater importance on the presence of trisomies.

Dr. Ken Shain of the Moffitt Cancer Center in Tampa, Florida, who was not involved in the study, agreed that these findings may further aid physicians in selecting appropriate treatment regimens for their patients based on their disease risks.

“Currently, most centers treat patients differently based on risk stratification. [From the results of this study], we may be able to identify an additional population of individuals in which we can avoid increased toxicity with equivalent efficacy by using [lower doses] of therapy,” said Dr. Shain.

Dr. Kumar and his colleagues acknowledged, however, that further research is needed to determine the impact of high-risk chromosomal abnormalities plus trisomies in myeloma patients treated with different therapies.

Chromosomal abnormalities are the result of structural changes in the chromosomes of a patient’s myeloma cells. These changes may occur through deletions, insertions, duplications, or movement ("translocation") of chromosomal regions.

A trisomy is a chromosomal abnormality where a person has three copies of a chromosome, instead of the regular two.

Myeloma patients may have trisomies that typically involve one or more of the odd numbered chromosomes 3, 7, 9, 11, 15, or 17. Previous research has shown that trisomies may be associated with better survival in myeloma patients.

On the other hand, past studies have shown that myeloma patients who possess the chromosomal abnormalities known as t(4;14), t(14;16), t(14;20), del17p, or monosomy 17 (one copy of chromosome 17) have poorer survival outcomes than patients who do not have these abnormalities. Patients with any of these chromosomal abnormalities are considered to have high-risk disease.

Myeloma patients who have one of these high-risk chromosomal abnormalities often have other chromosomal abnormalities, such as trisomies.

However, according to the study authors, it is unclear how the presence of multiple, concurrent chromo­somal abnormalities, especially the presence of both trisomies and translocations, affects the survival outcomes of myeloma patients.

Researchers from the Mayo Clinic in Rochester, Minnesota, and Scottsdale, Arizona, therefore, analyzed data from 484 multiple myeloma patients who were diagnosed with multiple myeloma between January 1, 2004, and December 31, 2009. All patients were seen at the Mayo Clinic within 90 days of their diagnosis. The median patient age was 65 years.

Using a technique called florescent in-situ hybridization (FISH), the researchers found that 97 percent of patients had at least one chromosomal abnormality.

The researchers categorized 24 percent of patients as high-risk patients based on their chromosomal abnormalities.

Of the 484 patients included in the analysis, 57 percent showed trisomies of at least one of the odd numbered chromosomes (3, 7, 9, 11, 13, 15, or 17). The most commonly observed trisomy was in chromo­some 9 (42 percent), followed by chromosomes 15 (37 percent), 11 (36 percent), 3 (33 percent), and 7 (27 percent).

Approximately 15 percent of patients had both high-risk translocations as well as trisomies.

As expected, standard-risk patients showed significantly longer median overall survival times at a median follow-up of three years (not yet reached) than high-risk patients (3.9 years).

The researchers then divided the high-risk patients into two groups based on whether or not they had a trisomy. They found that high-risk patients with a trisomy had significantly longer median overall survival times (not yet reached) compared to high-risk patients without a trisomy (three years).

Moreover, they found that none of the trisomies were associated with better outcomes than the others.

The researchers then created a new high-risk patient group that only included high-risk patients without a trisomy. High-risk patients with a trisomy were reclassified as standard-risk patients, along with the original standard-risk patients.

They found that the new high-risk group had a median overall survival of three years. The median overall survival of the new standard-risk group was not reached at the time of follow-up.

According to the researchers, it is unclear why trisomies improve the survival outcomes of high-risk myeloma patients, or why they appear frequently in myeloma cells.

They speculated that additional copies of odd-numbered chromosomes may increase the number of genes involved in the suppression of tumors or in the sensitivity of myeloma cells to anti-myeloma drugs.

Dr. Shain also speculated that trisomies provide an alternate pathway of development for myeloma cells that cause them to become less malignant than their normal modes of development.

“Trisomies may suggest an early or alternate transformational pathway in [the formation of myeloma cells], and myeloma cells that develop through this hypothetical pathway are less aggressive,” commented Dr. Shain.

For more information, please see the study in the journal Blood (abstract).