Evaluating factors associated with improved denosumab outcomes of patients with multiple myeloma

This study evaluated factors associated with improved outcomes of denosumab (Xgeva) compared to zoledronic acid (Zometa). 

The authors found that denosumab increased survival without cancer worsening in patients that planned to have an autologous stem cell transplant (ASCT) or those who previously received treatment with a proteasome inhibitor (PI). 

Multiple myeloma (MM) is a type of cancer happening in the bone marrow and it affects plasma cells. Patients with MM can receive an ASCT, in which healthy blood stem cells from the patient are injected into the bone marrow to replace the damaged cells. PIs such as bortezomib (Velcade) are a type of medication commonly used in MM.  PIs stop the proteasomes (proteins that get rid of damaged or unneeded proteins) from chewing up excess proteins. As a result, proteins build up in the cells and this leads to the death of cancer cells.

Despite improvements in treatment, patients with MM can experience osteolytic lesions (spots of damaged bone). These lead to skeletal-related events (SRE) such as spinal cord compression and fractures of bones. In order to prevent SRE, patients can be treated with bone-targeted drugs such as bisphosphonates (such as zoledronic acid; ZA) and denosumab. Denosumab is a targeted drug that blocks the action of osteoclasts (cells that degrade bone). 

A previous study showed that denosumab was also able to increase the survival without cancer worsening of patients with MM compared to ZA. However, it is not clear if this benefit is seen in all patients with MM and which factors impact this benefit of denosumab over ZA.

This study included 1718 patients with newly diagnosed MM. Patients were divided into two main groups. Group 1 included 930 patients that intended to have an ASCT. Group 2 included 788 patients that did not want or could not receive ASCT. Half of the patients in each group received ZA and half received denosumab. Patients also received double/triple therapy with or without a PI such as bortezomib. 

Patients in group 1 receiving denosumab had a longer average survival without cancer worsening (46.1 months) compared to those treated with ZA (35.7 months). Also, patients in group 1 that received either triple therapy or bortezomib-only treatment stayed for a longer time without cancer worsening with denosumab. 

In group 2, denosumab did not improve survival without cancer worsening (30.4 months) compared to ZA (34.7 months). 

Patients were then grouped according to their kidney function. In patients with a poor kidney function (creatinine clearance of 60ml/min or lower), there was no difference in survival without cancer worsening between denosumab and ZA. However, in patients with a good kidney function (creatinine clearance over 60 ml/min), denosumab showed improved survival without cancer worsening compared to ZA. Also, the benefit of denosumab over ZA was seen in patients younger than 70 years.

The authors showed that denosumab improves survival without cancer worsening in younger patients with MM and a good kidney function having an ASCT and who have received a PI-based triple therapy.

This study collected data from a bigger clinical trial. As the trial had different aims, not all the data necessary for this study were present.