Carfilzomib improves outcomes for previously treated multiple myeloma – a review

This study summarized findings on the treatment combination known as CRd (carfilzomib [Kyprolis], lenalidomide [Revlimid], and dexamethasone [Decadron]) for previously treated multiple myeloma. The study concluded that CRd is superior in improving progression and treatment response rates compared to available alternatives.

Advances in first-line treatments have improved response and survival rates among multiple myeloma patients. Carfilzomib is a type of targeted therapy that blocks the action of the protein proteasomes in cancer cells. The European Commission has recently approved carfilzomib in combination with the immunotherapy lenalidomide and the steroid drug dexamethasone for patients who have received at least one prior therapy. This treatment combination is commonly referred to as CRd. 

The aim of this study was to summarize findings on the safety and effectiveness of CRd.

A pivotal study on CRd included 792 mutliple myeloma patients who had undergone at least one prior therapy. Patients were randomly assigned to treatment groups. The average time to disease progression was 26.3 months in the group receiving CRd. This was significantly longer compared to 17.6 months among patients receiving only lenalidomide and dexamethasone (Rd). The overall response rate was 87.1% for CRd and 66.7% for Rd. In the CRd group, 32.8% of patients achieved a complete response or higher, compared to 9.4% in the Rd group.

Patients treated with CRd reported improved health-related quality of life over 18 cycles of treatment. The improvement was significantly greater compared to Rd from the 12th cycle of treatment onwards.

The most common serious side effects included low red and white blood cell counts, pneumonia, fatigue, high blood pressure, diarrhea, and lung infections.

Another study examined the role of carfilzomib in supportive care in 315 patients with 3 or more prior lines of treatments. Carfilzomib was associated with a higher overall response rate (19.1%) compared to low-dose steroid with optional chemotherapy (11.4%). No significant differences in overall survival or progression-free survival were noted.

Patients not responding to the proteasome-inhibitor bortezomib (Velcade) showed longer progression-free survival with CRd (22.3 months) than with Rd (19.4 months). Patients not responding to lenalidomide showed an average time to disease progression of 11.3 months with CRd compared to 9 months with Rd. Adding carfilzomib to treatment also improves outcomes in patients no longer responding to Rd.

Patients with heart disease or at high risk of heart failure may not be eligible to receive CRd. A study that excluded patients at high risk of heart failure reported increased incidences of cardiovascular events with CRd compared to Rd. Heart failure rates were higher with CRd (6.4%) versus Rd (4.1%). This also included heart failure (3.8% with CRd versus 1.8% with Rd). Incidences of heart disease were higher with CRd (5.9%) versus 4.6% for Rd;  including serious heart disease (3.3% with CRd versus 2.1% with Rd). Irregular heart beat occurred in 16.6% (CRd) and 15.2% (Rd) of patients. Disease of the heart muscle occurred in 1% (CRd) and 0.3% (Rd) of patients.

Authors concluded that CRd is superior in improving progression and treatment response rates compared to available alternatives for relapsed multiple myeloma.