Is carfilzomib effective with lenalidomide and dexamethasone in relapsed multiple myeloma?

This study compared the effectiveness of carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (Ozurdex) to lenalidomide and dexamethasone alone in patients with relapsed multiple myeloma. This study concluded that the addition of carfilzomib improved outcomes.

Survival rates for multiple myeloma have improved in recent years, but relapses are common. New therapies for the disease are needed. The standard regimen for both newly diagnosed and relapsed multiple myeloma is a combination of the steroid dexamethasone and lenalidomide. Lenalidomide is a therapy that stimulates the immune system to fight the myeloma cells. This combination in relapsed patients has been associated with an average time to disease progression of 11.1 months, and an overall response rate of 60%.

Carfilzomib 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. Carfilzomib alone led to a 23.7% response rate in relapsed patients or those who did not respond to treatment. It is not clear whether combining carfilzomib with lenalidomide and dexamethasone would further improve outcomes.

This study included 792 relapsed patients randomly assigned to one of two groups. Group 1 (396 patients) was treated with carfilzomib, lenalidomide, and dexamethasone. Group 2 (396 patients) was treated with lenalidomide and dexamethasone. Patients in group 1 were followed for an average of 32.3 months. Patients in group 2 were followed for an average of 31.5 months.

Average time to disease progression was 26.3 months in group 1 and 17.6 months in group 2. The risk of disease progression was 31% lower for group 1 compared to group 2. Two-year overall survival (time from treatment until death from any cause) was 73.3% for group 1 and 65% for group 2.

87.1% of group 1 responded to treatment, and 31.8% showed a complete response (no sign of disease). 66.7% of group 2 responded to treatment, and 9.3% showed a complete response.

69.9% of group 1 and 77.9% of group 2 stopped treatment, mostly due to disease progression. Serious side effects occurred in 59.7% of group 1 and 53.7% of group 2. These included difficulty breathing, heart problems, high blood pressure, and kidney failure.

This study concluded that adding carfilzomib to lenalidomide and dexamethasone significantly improved time to disease progression.