French researchers recently determined that the chromosomal abnor­mal­i­ties t(4;14) and del(13) are less common in older newly diagnosed myeloma pa­tients than in younger patients.

In contrast, the del(17p) abnormality was found to occur with a similar frequency across myeloma patients of all ages.

The researchers also found that the t(4;14) and del(17p) abnormalities have the same prognostic value in older patients as in younger patients.

Specifically, older patients with t(4;14) and del(17p) had shorter pro­gres­sion-free and overall survival com­pared to patients without those chro­mo­som­al abnormalities.

The del(13) abnormality, on the other hand, negatively impacted progression-free survival but did not have an impact on overall survival in older patients.

Based on their findings, the researchers recommend that all patients, regardless of age, should be tested for the t(4;14) and del(17p) abnormalities at diagnosis to assist doctors in prescribing effective treatment.

Background

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.

Previous studies have shown that certain chromosomal abnormalities, in particular t(4;14), del(17p), and 1q gain, negatively affect the survival of myeloma patients who have these abnormalities (see related Beacon ^[1] news).

The French investigators point out, however, that most of the findings regarding chromosomal abnormalities are based on data from patients under the age of 65 years, many of whom receive high-dose chemotherapy followed by autologous (own) stem cell transplantation as part of their initial therapy.

Among myeloma patients over the age of 65,  stem cell transplantation is less common -- particularly in Europe.

Study Design

The French investigators therefore retrospectively analyzed the records of 1,890 newly diagnosed multiple myeloma patients over the age of 65 years. The median patient age was 72 years.

The study authors do not specify exactly when the patients in their sample were diagnosed.  However, it ap­pears that many were initially diagnosed as early as the year 2000.

The researchers divided the 1,890 patients in their sample into two groups based on age: patients aged 66 years to 75 years (66 percent), and patients over the age of 75 years (34 percent).

Treatment information was available for 1,095 of the 1,890 patients in the researchers' sample.  These pa­tients had received a variety of different treatments.  Most were melphalan ^[2] (Alkeran)-based therapies, many of which also included a novel agent, such as thalidomide ^[3] (Thalomid), Velcade ^[4] (bortezomib), or Rev­limid ^[5] (lena­lido­mide).

All patients were tested for the t(4;14), del(13), and del(17p) chromosomal abnormalities at diagnosis using fluorescence in situ hybridization (FISH).

The investigators compared the data for these older patients to data based on a sample of 2,347 newly diag­nosed myeloma patients under the age of 66 years.

Results

The researchers found that the most common chromosomal abnormality at diagnosis for both of the older groups was del(13), followed by t(4;14) and del(17p).  The researchers stated that these findings are similar to those for patients under the age of 65 years.

However, the researchers found that the share of patients with del(13) and t(4;14) decreased with age.

The share of patients with the del(13) abnormality decreased from 45 percent in patients under 65 years of age to 44 percent in patients between 66 years and 75 years to 37 percent in patients above 75 years.

The researchers observed a similar trend in patients with the t(4;14) abnormality (14 percent to 11 percent to 8 percent).

On the other hand, the share of patients with the del(17p) abnormality remained stable at 6 percent across all age groups.

In addition, the researchers found that del(17p) and t(4;14) had a negative impact on both progression-free and overall survival of older myeloma patients.

The median progression-free survival was 11 months for patients with del(17p) and 14 months for patients with t(4,14), compared to 24 months for patients with­out these chromosomal abnormalities.

The differences were even more pronounced for overall survival. The median overall survival was 19 months for patients with del(17p) and 32 months for patients with t(4,14), compared to 50 months for patients with­out these chromosomal abnormalities.

The chromosomal abnormality del(13) had a small negative impact on progression-free survival, but it had no significant impact on overall survival in older patients.

The researchers note that previous studies have shown that Velcade-based treatments appear to improve outcomes in patients with the t(4;14) abnormality. However, the number of patients in the current analysis who were treated with Velcade was too small for the researchers to compare outcomes between Velcade-based and other therapies.

They add that no treatments have been shown to improve outcomes in patients with the del(17p) abnor­mal­i­ty.

In the discussion of their results, the authors of the study say that it is unclear why older myeloma patients have a lower incidence of the del(13) and t(4;14) abnormalities.

One potential explanation is that certain abnormalities, such as t(4;14), may accelerate the development of active (symptomatic) myeloma out of the earlier stages of the disease -- smoldering myeloma and mono­clo­nal gammopathy of undetermined significance (MGUS).

If this is the case, one would expect younger myeloma patients to have a higher incidence of abnormalities such as t(4;14), since the presence of the abnormalities would shorten the pre-symptomatic stages of mye­lo­ma.

For more information, please refer to the study in the Journal of Clinical Oncology ^[6] (abstract).