Results from a recent German analysis suggest that Velcade-based treatment both before and after stem cell transplantation leads to better survival outcomes than treatment without Velcade in multiple myeloma patients with a deletion in chromosome 17.

The German analysis used data from a Phase 3 clinical trial in which some patients with chromosomal abnormalities were treated with Velcade (bortezo­mib)-based therapy, while others were not.

For all types of chromosomal abnormalities, survival was similar or better for patients in the trial who received Velcade-based therapy.

In particular, though, patients with a deletion in chromosome 17 had significantly better survival when treated with Velcade.

Based on their results, the study authors recommend that patients with a deletion in chromosome 17 be treated long-term with Velcade.

Chromosomal abnormalities result from changes in the structure or number of an individual’s chromo­somes. These changes may occur through deletions, insertions, duplications, or movement of chromo­somal regions.

Previous research has shown that certain chromosomal abnormalities, such as the translocations t(4;14) and t(14;16) and deletions in chromosomes 13 and 17, are considered high-risk factors in multiple myeloma patients because these patients tend to have poorer prognoses.

Previous studies have indicated that Velcade-based therapies may improve the outcomes of patients with high-risk chromosomal abnormalities (see Beacon related news).  However, further research is needed to clarify whether these results apply to all types of high-risk chromosomal abnormalities and which Velcade-based regimens are best.

To further investigate the effect of Velcade in patients with high-risk chromosomal abnormalities, researchers in Germany retrospectively analyzed data from 354 newly diagnosed multiple myeloma patients who had participated in a Phase 3 trial at German institutions.

The median age of the participants was 57 years, and 97 percent of the patients had high-risk chromosomal abnormalities. The most common chromosomal abnormalities among the patients were gains in chromo­some 9 (57 percent), chromo­some 15 (52 percent), chromo­some 19 (52 percent), and chromo­some 11 (49 percent); deletions in chromo­some 13 (48 percent); and extra copies of chromo­somes (49 percent). 

Additional gains, deletions, and translocations also were observed.  In particular, 11 percent of participants had deletions in chromosome 17.

Patients were enrolled in the trial between 2005 and 2008.

During the trial, half of the participants were placed in a control group.  Patients in this group received three cycles of vincristine, doxorubicin (Adriamycin), and dexamethasone (Decadron) followed by stem cell transplantation. After stem cell transplantation, patients in this group received maintenance therapy with thalidomide (Thalomid) for two years.

The other half of the patients in the trial were placed in a Velcade-treatment group.  These patients received Velcade, doxorubicin, and dexamethasone followed by stem cell transplantation and Velcade as mainte­nance therapy for two years.  The dosing of the Velcade maintenance regimen was 1.3 mg/m² once every two weeks.

The median follow-up time was 41 months.

Among all of the participants, the median progression-free survival time was 33.4 months and the median overall survival had not yet been reached.

The researchers found that deletions in chromosomes 13 and 17, the translocation t(4;14), and a gain in chromosome 1 had a negative impact on both progression-free and overall survival.

Of all analyzed chromosomal abnormalities, deletions in chromosome 17 had the biggest effect on outcome. Patients without the deletion had a median progression-free survival of 36 months, compared to 18 months for patients with the deletion. The researchers observed similar results for the three-year overall survival rates (83 percent for patients without the deletion, compared to 36 percent for patients with the deletion).

Across all of the participants in the study, those who received Velcade-based therapy had longer progression-free survival times (36 versus 31 months) and higher three-year overall survival rates (84 percent versus 73 percent) than patients in the control group.

However, patients with a deletion in chromosome 17 benefited the most from Velcade-based treatment.

Specifically, patients with a deletion in chromosome 17 who received Velcade-based treatment demonstrated a significantly better progression-free survival time (26 months) than those in the control group (12 months). The three-year overall survival rate was also significantly higher in patients who received Velcade (69 percent) than in those in the control group (17 percent).

A previous study showed that Velcade only prior to stem cell transplantation was not superior to standard therapy for patients with a deletion in chromosome 17.

The researchers therefore suggested that the long-term use of Velcade could significantly reduce the negative effects of this chromosomal abnormality on progression-free and overall survival.

However, the study authors pointed out that thalidomide as maintenance therapy is associated with worse overall survival outcomes in patients with high-risk chromosomal abnormalities.  As a result, the positive effect of Velcade maintenance therapy may be overstated in these results. They therefore recommended further studies to confirm their findings.

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