Can daratumumab, bortezomib, and dexamethasone be used in the treatment of relapsed or refractory multiple myeloma with high cytogenetic risk?

This study assessed the use of daratumumab (Darzalex) plus bortezomib (Velcade)/dexamethasone (Dexasone) or D-Vd versus bortezomib/dexamethasone (Vd) alone as a treatment for patients with high-risk multiple myeloma (MM). The authors found that D-Vd was effective and showed good tolerability in the treatment of MM regardless of the risk status of patients. 

MM is a form of cancer that comes from plasma cells (a type of white blood cell). Despite new treatments being developed MM remains incurable. MM can become resistant to therapies (refractory) and patients can often relapse (cancer occurring again) after treatment. Patients with high cytogenetic (CG) risk develop RRMM at a higher rate when compared to low-risk MM patients. CG refers to genetic abnormalities that make cancer more likely not to respond to standard treatment.

Daratumumab is a monoclonal antibody (proteins that function in the immune system) approved for the treatment of MM. It can be used as a single therapy or in combination with Vd. D-Vd has shown good response in patients with relapsed or refractory (RR) MM compared to Vd alone. However, whether this combination also improves survival in patients with high CG risk remains under investigation.

There were a total of 498 patients in this study. 251 were in the D-Vd group and 247 patients received Vd alone. 356 patients (71%) underwent CG testing. 40 patients in the D-Vd group and 35 patients in the Vd group were classified as high-risk. There were 141 patients in the D-Vd group and 140 in the Vd group classified as standard CG risk. The average follow-up in this study was 40.0 months. 

In patients with standard CG risk, D-Vd significantly prolonged survival without cancer worsening by 74%. The average survival without cancer worsening in this group was 16.6 months with D-Vd treatment compared to 6.6 months in the Vd group. Survival without cancer worsening was also 59% higher with D-Vd vs Vd in the high-risk group. Patients with high CG risk treated with D-Vd had a survival without cancer worsening of 12.6 months compared to 6.2 months in Vd group.

The response rate to the treatment was higher with D-Vd compared to Vd alone in both standard risk (84% vs 62%) and high-risk (85% vs 56%) patients.

Side effects occurred in at least 25% of patients. Some of the side effects experienced by patients were low blood cell counts, diarrhea, and upper respiratory infection. There were similar numbers of patients in the standard-risk and high-risk groups that stopped both types of treatments due to side effects. 

The authors concluded that D-Vd was effective and well tolerated when compared to a Vd only in the treatment of MM regardless of CG risk status. 

This study was funded by Janssen Research & Development, LLC, the manufacturers of daratumumab. There were multiple methods for measuring CG risks in this study and not all patients underwent CG risk measurements. This might have affected the results.