First of all bone disease is the most common complication of multiple myeloma. In approximately 80% of patients at diagnosis we see lytic lesions and many of the patients have skeletal related events and we define these like pathological fractures made in the vertebra. 25% of patients at diagnosis have a fracture, a pathological fracture. You understand that this creates a lot of pain for our patients but also we have hypercalcaemia of malignancy, we have spinal cord compression sometimes because of plasma cytomas or vertebra fractures and may, of course, need radiation or surgery to the bone. These are all skeletal related events that increase the morbidity and, of course, impair the quality of life of our patients. So bone disease is one of the most important complications of multiple myeloma to be treated.
How do you go about treating this?
The current management of multiple myeloma bone disease is based on bisphosphonate use, mainly zoledronic acid and to a lesser extent of pamidronate. This is mainly because of the MRC IX study comparing zoledronic acid and clodronate which showed an overall survival advantage in favour of zoledronic acid. So the majority of the physicians are using zoledronic acid although in other countries like the Nordic ones pamidronate is also used. The two drugs, zoledronic acid and pamidronate, have showed comparable efficacy in a phase III study but in the era of conventional chemotherapy.
The bisphosphonates are used in all patients who need active treatment, meaning in all patients with symptomatic myeloma. The treatment duration is approximately two years for all patients but then if the patients are in CR or very good partial response then the treating physician can stop the administration of bisphosphonates. If the patients have achieved only PR or less than that then the bisphosphonates have to be continued. Also at the relapse of the disease bisphosphonates have to be reinitiated.
We say that we recommend to stop the bisphosphonates because of some side effects like the renal impairment and the osteonecrosis of the jaw. With the new drug denosumab, which is a monoclonal antibody against RANK ligand which is a potent activator of the osteoclast, so denosumab is inhibiting the osteoblast function, we believe that we may have a solution for renal impairment patients because in the study that compares denosumab with zoledronic acid we have seen much fewer renal problems with denosumab and adverse events compared to zoledronic acid. So I believe that for renal impairment patients denosumab will give a solution while zoledronic acid and pamidronate are not recommended for patients with creatinine clearance below 30.