Are lenalidomide, bortexomib, and dexamethasone effective with stem cell transplantation in myeloma?

This study examined whether combined treatment with lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVD) is effective without stem cell transplantation (SCT) in patients with multiple myeloma. The authors concluded that RVD followed by SCT led to longer times before disease progression compared to RVD alone. There was no difference in overall survival (time from treatment until death from any cause).

The standard treatment option for patients up to age 65 with multiple myeloma has been high-dose chemotherapy followed by stem cell (immature blood cell) transplantation. This treatment, however, is associated with many side effects.

Newer treatments for multiple myeloma include lenalidomide and bortezomib. Lenalidomide is a therapy that stimulates the immune system against cancer cells. Bortezomib is a proteasome inhibitor. The proteasome is involved in cancer cell growth and death. Blocking the proteasome can decrease cell growth and increase cell death.

These therapies, combined with the steroid dexamethasone, have led to improved response rates and survival. It is not clear whether chemotherapy and SCT should still be considered a first-line treatment for myeloma patients under the age of 65. 

This study included 700 patients who were randomly assigned to one of two groups. The RVD-alone group was treated with RVD during induction (the first treatment phase). This was followed by five more cycles of RVD during consolidation (the second treatment phase). The SCT group was also treated with RVD during induction, but then received high-dose chemotherapy and SCT. All patients received long-term lenalidomide treatment to prevent relapse. This is known as maintenance therapy. Patients were followed for 43–44 months.

A complete response refers to when there is no sign of active disease following treatment. 59% of the SCT group achieved a complete response. In comparison, 48% of the RVD-alone group achieved a complete response. A good response refers to when signs of disease have dramatically decreased. A good or complete response was seen in 78% of the SCT patients in the consolidation phase. This was significantly more the 69% of RVD-alone patients.

Response rates were also higher following maintenance in the SCT group (85%) compared to RVD-alone (76%). No remaining myeloma cells (known as minimal residual disease) were found in 79% of the SCT group. This was compared to 65% of the RVD-alone group.

Patients in the SCT group were 35% less likely to experience disease progression over the follow-up. There was no significant difference in overall survival.

Rates of seriously low white blood cell levels (neutropenia) occurred in 92% of the SCT group. 47% of the RVD-alone group experienced this effect. Rates of gastrointestinal issues and infections were also higher following SCT.

This study concluded that RVD therapy followed by stem cell transplantation was associated with significantly longer time to disease progression than RVD therapy alone. However, the rates of overall survival were not significantly different.