A recent study showed that relapsed and therapy-resistant multiple myeloma patients with an abnormality on chromosome 1, called 1q21 gain, did not respond as well to single-agent Velcade treatment in comparison to patients who lack this chromosomal abnormality.

The study found that the median duration of response, progression-free survival, and overall survival were significantly lower among patients with the 1q21 gain abnormality.

Chromosomal abnormalities are the result of unbalanced changes to the structure of a chromosome, which may occur through deletions, insertions, duplications, or movement of chromosomal regions. They are considered high-risk factors in multiple myeloma and may render patients less responsive to certain treatments.

However, previous studies have found that relapsed or refractory myeloma patients with the chromosomal abnormalities del(13q) (a deletion in a region of chromosome 13) or t(4;14) (a translocation between chromosomes 4 and 14) respond as well to Velcade ^[1] (bortezomib) treatment as patients without those chromosomal abnormalities.

In addition to del(13q) and t(4;14), del(17p) (a deletion in a region of chromosome 17), del(1p21) (a deletion in a region of chromosome 1), and 1q21 gain (duplication or movement of a region in chromosome 1) are also considered high-risk factors in myeloma patients.

According to Dr. Hong Chang, the lead author of this study, the 1q21 gain occurs in 35 to 45 percent of multiple myeloma cases and is often associated with poor prognosis and disease progression in newly diagnosed patients. It is also associated with a poor prognosis for patients receiving high-dose therapy and stem cell transplants.

The response of relapsed or refractory myeloma patients with del(17p) or 1q21 gain to Velcade treatment has not, however, been carefully examined. 

The goal of this study was to evaluate the response to Velcade treatment in relapsed and refractory multiple myeloma patients with at least one of the following five chromosomal abnormalities: del(13q), t(4;14), del(17p), del(1p21), or 1q21 gain.

A total of 85 patients underwent genetic testing to determine the presence of chromosomal abnormalities. Of these patients, 32 percent did not have any of the five abnormalities, while 2 percent had all five.

Velcade was administered as a single-agent therapy to 74 percent of patients. It was administered with steroids to 20 percent of patients, and 6 percent of patients received it with thalidomide ^[2] (Thalomid) and dexamethasone ^[3] (Decadron).

Patients with a 1q21 gain had significantly lower median duration of response, median progression-free survival, and overall survival.

There was no significant difference in the responses of patients who had genetic abnormalities other than 1q21 gain.

Median duration of response was 9.1 months for patients without the 1q21 gain compared to 5.9 months for patients with the 1q21 gain.

Median progression-free survival amounted to 7.3 months for patients without the 1q21 gain compared to 2.3 months for patients with the 1q21 gain.

Patients without the 1q21 gain had a median overall survival of 24.6 months, while those with the 1q21 gain had an overall survival of 5.3 months.

In an email correspondence with the Beacon, Dr. Chang explained that although the 1q21 gain may adversely affect progression-free and overall survival, it did not affect the response rates of the patients in this study.

The researchers cautioned, however, that given the small number of participants in this study, larger trials will be needed to confirm the importance of the 1q21 gain in Velcade-treated patients. 

They also noted that further studies will be needed to determine the response of patients with the 1q21 gain to first line Velcade treatment. 

For more information about this study, please see the study in Leukemia Research ^[4] (abstract).