A new study provides useful, if somewhat dated, insight into the efficacy and safety of Velcade combined with dexa­metha­sone to treat relapsed or refractory multiple myeloma.

The retrospective study, which was carried out using data from a single center in Italy, included patients who had a median of two previous ther­a­pies.

In these patients, the combination of Velcade ^[1] (bortezomib) and dexa­meth­a­sone ^[2] (Decadron) had an overall response rate of 55 percent, and a complete re­sponse rate of 19 percent.  Median overall survival from the start of treatment was 22 months.

The combination therapy was generally safe, although many patients (78 percent) experienced some de­gree of peripheral neuropathy (pain, tingling, or loss of sensation in the extremities).

The high share of patients who experienced peripheral neuropathy was most likely due to the fact that most patients in the study had previously been treated with thalidomide ^[3] (Thalomid), which often has peripheral neuropathy as a side effect.

The survival data from this study can be expected to provide a minimum estimate for the median survival mye­loma patients today can expect when at a similar point in their own treatment.  Patients in the current study did not have access to newer therapies, such as Kyprolis ^[4] (carfilzomib) and Pomalyst ^[5] (pomalidomide, Imnovid), that can now be used to extend survival after several previous lines of therapy.

In addition, not all patients in the new study had access to Revlimid ^[6] (lenalidomide) as a treatment option, since it was not yet approved in Italy during a portion of the time period covered by the study.

Background

Velcade is currently approved in the United States and Europe for the treatment of multiple myeloma, both newly diagnosed as well as relapsed and refractory.

The clinical trials that initially led to Velcade’s approval for relapsed and refractory myeloma studied Velcade compared to high-dose dexa­metha­sone.  In some of these studies, patients who experienced a suboptimal response on Velcade alone could have dexa­metha­sone added to their treatment regimen.

The authors of the current study note, however, that in current clinical practice, Velcade is typically combined with dexa­metha­sone, rather than used alone.

Yet, according to the authors, little is known about the long-term efficacy of Velcade plus dexa­metha­sone in relapsed and refractory myeloma patients.

Study Design

Researchers from the Seragnoli Institute of Hematology in Bologna, Italy, analyzed the records of 85 re­lapsed and refractory multiple myeloma patients who had received a combination of Velcade and dexa­meth­a­sone as a salvage therapy between 2004 and 2011.

The median patient age was 58 years. The patients had received a median of two prior therapies.  Most of the patients (84 percent) had previously been treated with thalidomide, and most also had received an autologous (own) stem cell transplant (85 percent).

None of the patient had prior exposure to Velcade, and just a few patients (4 percent) had been previously treated with Revlimid.

Each patient received 1.3 mg/m² of Velcade on days 1, 4, 8, and 11 of a three-week treatment cycle. Patients also received 20 mg of dexa­metha­sone on the day of and day after Velcade administration.

Study Results

After a median follow-up of 22 months, the overall response rate was 55 percent, with 19 percent achieving a complete response, 7 percent a near complete response, 9 percent a very good partial response, and 20 percent a partial response.

The median time to achieving a complete response was 3.3 months. The median duration of response was 8 months.

The researchers note that patients who were treated at first relapse – that is, with just one previous line of therapy – had a significantly higher chance of achieving a complete response, compared to patients treated at second or later relapse (25 percent versus 16 percent, respectively).

The presence or absence of kidney damage had no effect on the response rate, according to the study authors.

The median progression-free survival time was 8.7 months, and the median overall survival time was 22 months.

As in a number of other studies, the investigators found that depth of response was associated with im­proved progression-free and overall survival. Patients who achieved a complete response had signifi­cant­ly longer progression-free survival (13 months) and overall survival (41 months), compared to patients who did not achieve a complete response (7 months and 20 months, respectively).

According to the researchers, the Velcade-dexa­metha­sone combination had an acceptable safety profile.

The most common side effects were peripheral neuropathy (78 percent), gastrointestinal symptoms such as diarrhea and nausea (52 percent), and low platelet counts (41 percent).

Although peripheral neuropathy was a common side effect, the researchers note that only 6 percent of the patients discontinued treatment due to side effects of any kind.

According to the investigators, the rate of peripheral neuropathy could be reduced by switching to once week­ly Velcade infusions or by using subcutaneous Velcade.

For more information, please refer to the study in the journal Annals of Hematology ^[7] (abstract).