Results from a retrospective Canadian study indicate that combination therapy with Revlimid, Velcade, and dexamethasone is effective for certain heavily pretreated multiple myeloma patients. The findings show that nearly 50 percent of patients with advanced myeloma respond to the three-drug therapy.

The study investigators point out that although most patients with advanced myeloma progress quickly after therapy with Revlimid ^[1] (lenalidomide), Velcade ^[2] (bortezomib), and dexamethasone ^[3] (Decadron), particularly those with high-risk myeloma, some patients experience a “considerable benefit.”

They also note that side effects in this heavily pretreated patient population are common but manageable.

This three-drug regimen, commonly referred to as RVD or VRD, has already been shown to be effective in newly diagnosed as well as relapsed and refractory myeloma patients.

In a Phase 1/2 study of newly diagnosed myeloma patients, all participants responded to treatment with RVD (see related Beacon ^[4] news).

Furthermore, findings from a Phase 2 study showed that 84 percent of relapsed and refractory myeloma patients who had received between one and three prior treatment regimens responded to RVD (see related Beacon ^[5] news).

However, according to the Canadian researchers, the regimen has not yet been studied in people with heavily relapsed and refractory (advanced) myeloma.

In this retrospective study, investigators reviewed the records of 30 patients with advanced myeloma who were treated with RVD at the Princess Margaret Hospital in Toronto between March 2009 and December 2011. The patients had received a median of three prior therapies. Their median age at the start of RVD therapy was 57 years.

The majority of the patients had received Revlimid, Velcade, or an autologous stem cell transplant in the past (73 percent, 80 percent, and 83 percent, respectively). Moreover, 26 percent of patients had received both Revlimid and Velcade as part of prior therapies.

After a median of five RVD treatment cycles, the overall response rate was 47 percent.  Specifically, 10 percent of patients achieved a very good partial response and 37 percent achieved a partial response.  An additional 13 percent had stable disease.

The median progression-free survival time was three months and was similar regardless of previous exposure to Revlimid or Velcade .

In particular, the median progression-free survival time was 3.0 months for patients who had previously been treated with Revlimid and 2.3 months for those who had not previously received Revlimid.

In addition, the median progression-free survival time was 2.9 months for patients who had previously been treated with Velcade and 3.4 months for those who had not.

In contrast, high-risk myeloma had a significant impact on progression-free survival.  Patients with high-risk multiple myeloma had a much shorter progression-free survival time than those without high-risk factors (0.6 months versus 4.8 months, respectively).

The median overall survival was 7.6 months but only 2.5 months for patients with high-risk myeloma.

About a quarter (26 percent) of the patients experienced serious or life-threatening side effects that the study investigators described as manageable.

The most common side effects were low red blood cell counts (87 percent), low platelet counts (70 percent), and low white blood cell counts (70 percent).

To manage these side effects, 57 percent of patients required red blood cell or platelet transfusions. Also, 27 percent of patients received granulocyte colony-stimulating factor to increase their white blood cell counts.

Prior to treatment with RVD, 80 percent of patients had mild to moderate peripheral neuropathy (pain, tingling, or loss of feeling in the extremities due to nerve damage). However, the neuropathy did not worsen in any patients after RVD treatment.

For more information, please refer to the study in the journal Leukemia and Lymphoma ^[6] (abstract).