Myeloma specialists from the Czech Republic have published clinical trial results that shed further light on chromosomal abnormalities and their impact on survival in newly diag­nosed multiple myeloma patients.

Specifically, the researchers found that patients with three or more chromos­omal abnor­malities, a gain in the 1q21 region, or the trans­location t(4;14) have reduced survival compared to patients without such abnormalities.

According to the researchers, their findings highlight the importance of chromosomal abnormalities when considering treatment options for myeloma patients.

They note, however, that their findings need to be confirmed in a pro­spective, randomized trial that includes one or more novel agents.

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 of chromosomal regions. Cells with three or more abnormalities in their chromosomes are considered to have a complex karyotype.

Chromosomal abnormalities have been an area of intensive research.  Some abnormalities can be a sign that a patient's myeloma may be less responsive to certain treatments (see related Beacon ^[1] articles).

To determine the frequency of the most common chromosomal abnormalities and their effect on treatment outcomes in newly diagnosed multiple myeloma patients, the Czech researchers retrospectively analyzed data from patients who had participated in the Phase 3 CMG2002 trial.

The CMG2002 trial enrolled 542 newly diagnosed multiple myeloma patients in the Czech Republic from 2002 to 2007.

All patients in the trial received induction therapy with vincristine ^[2] (Oncovin), doxorubicin ^[3] (Adriamycin), and dexamethasone ^[4] (Decadron) followed by high-dose melphalan ^[5] (Alkeran) and an autologous stem cell transplant.

Patients were then randomized to receive either consolidation therapy and (eventually) maintenance therapy, or maintenance therapy alone.

In the "consolidation plus maintenance therapy" arm of the trial, patients received consolidation therapy consisting of cyclophosphamide ^[6], etoposide ^[7], and dexamethasone administered for four days in months 4, 8, 12, and 16 after the patient's transplant, followed by weekly subcutaneous interferon ^[8] injections beginning in the 18th month after transplant (until relapse).

In the "maintenance therapy only" arm of the trial, patients received weekly subcutaneous interferon injections after their stem cell transplant and until relapse.

Data on chromosomal abnormalities was available for 207 of the 542 study participants. The median patient age was 57 years.

The most common chromosomal abnormality was the deletion del(13q) (53 percent of patients), followed by a gain in the region 1q21 (46 percent), the translocations t(4;14) (23 percent), and t(11;14) (19 percent).

The least common chromosomal abnormality was the deletion del(17p), which was found in 7 percent of patients. Nineteen percent of patients had a complex karyotype.

Overall, the researchers found no difference in overall response rates in patients with chromosomal abnormalities compared to those without them.

However, the differences in survival for certain chromosomal abnormalities were significant.

The researchers found that patients with complex karyotypes had a significantly shorter time to disesase progression (17.5 months) than those with normal karyotypes (32.1 months).  Similarly, the overall survival for patients with complex karyotypes was 17.5 months, while the median overall survival for patients with normal karyotypes has not been reached.

In patients with t(4;14), researchers found a shorter time to disease progression compared to those without t(4;14) (18.0 months versus 36.2 months, respectively).  Overall survival was also negatively affected by t(4;14), with a median of 33.3 months for patients with the translocation compared to 60.7 months for those without it.

Researchers also found that patients with a gain in the region 1q21 had significantly worse outcomes than those without it.  Patients identified with 1q21 had a median time to disease progression of 21.3 months compared to 32.2 months for those without it.  The median overall survival in the gain of 1q21 subgroup was 30.4 months while it had not yet been reached for those without it.

The researchers pointed out that patients with both t(4;14) and complex karyotypes had very poor prognoses, with an median overall survival of 13.2 months.

The authors of the current study believe their results are a useful addition to the literature on chromosomal abnormalities and their impact on myeloma treatment and prognosis.

The authors accept, however, that some caution should be used in interpreting their results.  None of the patients in the Czech trial were treated with novel myeloma treatments such as thalidomide ^[9] (Thalomid), Velcade ^[10] (bortezomib), or Revlimid ^[11] (lenalidomide).  Yet these drugs are now regularly used in the treatment of newly diagnosed myeloma patients.

For more information, please see the study in the journal Leukemia & Lymphoma ^[12] (abstract).

Additional Information About Chromosomal Abnormalities

Each person’s genetic material is stored in chromosomes. Humans normally have two copies of 22 different chromosomes as well as two sex chromosomes (XX for women and XY for men).

Every chromosome has two regions, a short region (p) and a long region (q), and specific positions on the chromosome are numbered.

Therefore, 17p13 would refer to position 13 of the short region of chromosome 17.

There are a number of different types of chromosomal abnormalities. The most common chromosomal abnormalities related to myeloma include:

Deletion – A part of a chromosome is missing. For example: del(17p13) would mean that on chromosome 17, position 13 of the short arm is missing.

Translocation – A portion of one chromosome is transferred to another chromosome, or two chromosomes swap portions. For example, t(4;14) means that chromosomes 4 and 14 have swapped some of their genetic material.

Gain – There is an extra copy of a chromosome or part of a chromosome. For example: +1q21 would mean that this person has an extra copy of position 21 of the long region of chromosome 1.