Results from a Polish study suggest that a gain in chromosome 1, called 1q21 gain, must be accompanied by other chromosomal abnormalities to negatively affect prognosis in newly diagnosed multiple myeloma patients on thalidomide therapy.

Based on their findings, the Polish researchers conclude that thalidomide (Thalomid)-based regimens may not help overcome the negative impact of the 1q21 gain on patient survival when multiple chromosomal abnormalities are present.

“The key message [from our study] is that accumulation of adverse genetic abnormalities significantly affects the survival of multiple myeloma patients,” said Dr. Norbert Grzasko, a researcher at the Department of Hemato-Oncology and Bone Marrow Transplantation at the Medical University of Lublin in Poland and lead author of the study. “ [The accumulation of such genetic abnormalities] makes thalidomide less efficient than in the presence of one abnormality,” he added.

According to Dr. Rafael Fonseca of the Mayo Clinic in Arizona, who was not involved with the study, the results are consistent with those from other previous studies and are unlikely to cause any changes in the ways myeloma patients are treated in the short term.

Chromosomal abnormalities are changes in the number or structure of chromosomes (bundles of genetic material). Changes may occur through deletions, insertions or gains, duplications, or movement of chromosomal regions.

Previous studies have shown that multiple myeloma patients frequently have chromosomal abnormalities in their myeloma cells. Examples of common chromosomal abnormalities in multiple myeloma include deletions in chromosomes 13 and 17, translocations involving chromosome 14 and another chromosome, and deletion or gain of a fragment in the long arm of chromosome 1 (±1q21).

More than one such abnormality can be present in an individual with multiple myeloma. The type of chromosomal abnormality or abnormalities can determine how the patient responds to a particular treatment.

In the current study, Polish researchers sought to understand how the 1q21 gain affects response to thalidomide-based regimens, both when it is present by itself and in combination with other chromosomal abnormalities. Other studies so far have yielded conflicting results on the effect of the 1q21 gain on multiple myeloma prognosis.

A total of 84 newly diagnosed multiple myeloma patients participated in the study. The median patient age was 60 years, and 26 percent were above 65 years of age at the time of diagnosis. About half (49 percent) of study participants had advanced myeloma.

Bone marrow samples were collected from patients and examined for chromosomal abnormalities.

During induction therapy, patients younger than 65 years received treatment with cyclophosphamide (Cytoxan), thalidomide, and dexamethasone (Decadron), while patients ages 65 and older received melphalan (Alkeran), prednisone, and thalidomide. Thirty three percent of all study participants subsequently received autologous stem cell transplants.

The median follow-up time was 15 months.

Results from examination of bone marrow samples showed that 48 percent of patients had a 1q21 gain. Among these, 75 percent had additional chromosomal abnormalities, such as deletions del(13q14) and del(17p13) and translocation t(4;14).

The researchers found that the presence of the 1q21 gain negatively affected response to thalidomide-based therapy: 56 percent of participants with the 1q21 gain responded to induction therapy, compared to 73 percent of participants without the 1q21 gain.

Patients with the 1q21 gain had shorter progression-free and overall survival times (14 months and 25 months, respectively) than patients without it (33 months and 42 months, respectively).

The researchers then categorized participants with the 1q21 gain into those with and without additional chromosomal abnormalities and examined survival.

They found that progression-free and overall survival times of participants with the 1q21 gain alone were comparable to those of individuals without the 1q21 gain.

However, when participants had other chromosomal abnormalities in addition to the 1q21 gain, progression-free and overall survival times were significantly shorter (9 months and 16 months, respectively).

Dr. Grzasko noted that he and his colleagues will continue to investigate the influence of chromosomal abnormalities on outcome in myeloma patients, especially those with numerous changes. To that effect, they will expand the study group and collect data from about 250 myeloma patients treated with thalidomide. In addition, they will prolong the observation period of the study.

For further information, please see the study in Leukemia and Lymphoma (abstract).