The combination of Velcade with Revlimid-dexamethasone treatment may help overcome the poor prognostic factors with certain chromosomal abnormalities more so than Revlimid-dexamethasone alone.

However, both treatment combinations were associated with an inferior response in patients with a deletion in chromosome 17. Additionally, prior resistance to thalidomide, increases in certain enzyme levels, and the presence of tumor cells outside of the bone marrow were also associated with poor outcomes in response to Revlimid-dexamethasone with or without Velcade.

In this recently published study, Greek researchers compared the efficacy of Revlimid ^[1] (lenalidomide)-Velcade ^[2] (bortezomib)-dexamethasone ^[3] (Decadron) (RVD) treatment to Revlimid-dexamethasone (RD) treatment in relapsed or therapy-resistant (refractory) multiple myeloma patients.

A prior Phase 2 clinical trial showed that RVD treatment increased response rates compared to RD treatment alone in relapsed and refractory myeloma patients.

It is unknown, however, whether RVD treatment can overcome the poor outcomes associated with chromosomal abnormalities in this subset of patients.

The Greek researchers therefore included pre-treated relapsed and refractory myeloma patients with a variety of chromosomal mutations in their study.

Since Velcade is known to cause nerve damage, patients with severe nerve damage, a result of prior treatment, were given the RD combination without Velcade. Patients who had milder nerve damage received the RVD treatment. A total of 50 patients received RD, and 49 patients received RVD.

The response rates and the quality of responses were similar between RVD and RD-treated patients, with 63 percent and 61 percent of patients, respectively, achieving at least a partial response.

Response rates were lower in patients with high-risk chromosomal abnormalities in both treatment groups.  However, 55 percent of patients with chromosomal abnormalities responded when treated with RVD compared to 31 percent of patients treated with RD.

Further analysis revealed that a deletion in chromosome 17, prior thalidomide resistance, the presence of plasma cell tumors outside the bone marrow, and increased levels of an enzyme responsible for processing lactate were all associated with a poor response to both RVD and RD treatment.

The time to disease progression in both RVD and RD treatment groups (7 months and 9 months, respectively) were not statistically different. However, patients with high-risk chromosomal abnormalities had a significantly lower time to disease progression of 5.6 months. Patients with a deletion in chromosome 17 had the shortest time to disease progression (2 months).

Researchers did not observe any difference in overall survival among patients treated with RD or RVD. However, patients with chromosomal abnormalities who received RD treatment showed shorter overall survival than patients with chromosomal abnormalities who received RVD treatment.

The most common side effect of treatment was nerve damage to the extremities. This was more common in RVD-treated patients, with 66 percent of patients suffering from nerve damage over the course of treatment.  Of those treated with RD therapy, 30 percent experienced a worsening of their already existent nerve damage.

The researchers suggested that more clinical trials be conducted to determine the optimal treatment sequence of novel agents in patients with chromosomal abnormalities.

For more information, please see the study in Leukemia ^[4] (abstract).