This afternoon in the discussion I was talking about the treatment of bone disease and how bone disease affects patients with multiple myeloma. I was primarily concentrating on the therapeutic armoury from the point of view of drugs rather than interventional treatments. Initially we started off discussing the incidence of bone disease in multiple myeloma patients, that probably between 60-70% of patients have bone disease at diagnosis and by the time patients have gone through their treatment pathway their bone disease is almost universal. It clearly causes significant problems with morbidity, mortality and healthcare resource utilisation and it’s this area that we need to be targeting with the new agents.
What are the current therapeutic options?
First of all I went through the present guidance that is available. This has really evolved before denosumab became available which is the new anti-RANK ligand antibody available from Amgen. This recommends the use of the second generation aminobisphosphonates, specifically zoledronic acid, for the treatment of patients with bone disease or for any patient with myeloma who has started active treatment.
We looked at some of the history for the bisphosphonates going all the way back to the 1980s and the 1990s, quite some time ago now, looking at first generation bisphosphonates, such as clodronate, and where they may still have some utility. But we also covered some of the limitations of bisphosphonates and some of the problems that patients get with these drugs.
Then when we completed that we looked at the new 482 study recently published in The Lancet Oncology, specifically with the treatment of multiple myeloma using denosumab.
What did that study reveal?
That was probably the largest international study in this area that has been performed. What it showed, or what it was powered to show, was that denosumab was non-inferior to zoledronic acid which is the present standard of care. It also showed that the side effect profiles were very similar. It showed that there was a delay in the first skeletal related event in those patients that were treated with denosumab. It also suggested that there was an increase in progression free survival in those patients that were treated with denosumab but a very similar overall survival.
Will denosumab become the standard treatment of choice?
Denosumab is a very attractive option, particularly with those patients who have renal failure with creatinine clearances of less than 30, simply because the aminobisphosphonates are not licensed in this area but also because denosumab specifically targets RANK ligand which is the final common pathway in osteoclast production and osteoclast function and osteoclasts to the cells which cause most of the problems in myeloma bone disease.
What other possibilities are on the horizon?
The most promising thing in the future is the use of anabolic agents. Effectively the bisphosphonates and also denosumab are what we would refer to as anti-catabolic agents, so they stop bone destruction. However, the lytic bone disease in myeloma, only a very low percentage of patients with lytic bone disease actually get any recovery in that bone disease. So what we’re doing by treating with bisphosphonates is simply preventing further loss and even those are not perfect. What I would like to see in the future is the combination of anabolic agents, i.e. agents which increase osteoblast activity and help to repair bone disease, and hopefully combining those with some of the anti-catabolic agents.