An innovative clinical trial led by researchers at Garvan and St Vincent’s Hospital Sydney is recruiting participants to test whether a drug for osteoporosis could help rebuild bones eroded by multiple myeloma. This incurable blood cancer, characterised by an overproduction of abnormal plasma cells in the bone marrow, affects approximately 1,800 Australians each year and leaves 80% with bone lesions or thinning.
Bone deteriorated by multiple myeloma is regenerated after treatment with romosozumab (right) in a mouse model. Image credit: Garvan Institute
The first-of-its-kind study in Australia will evaluate romosozumab, an antibody therapy already approved for fracture prevention in osteoporosis, to determine if it can also restore the health of bones weakened by multiple myeloma. The drug counters the effects of a sclerostin protein, which blocks bone formation and can be found in high levels in myeloma patients.
“We have found that even while undergoing treatment with medications intended to slow down the process of bone breakdown, 45% of myeloma patients still face skeletal problems including fractures. These skeletal complications can lead to significant symptoms for patients, including pain, and are associated with an increased risk of death,” says Dr Georgia McCaughan, Staff Specialist Haematologist at St Vincent’s Hospital Sydney and Senior Research Associate at the Garvan Institute, who is leading the trial.
Exploring the regenerative capacity of antibody therapy in myeloma bone disease
Professor Peter Croucher, Head of the Bone Biology Lab at Garvan and co-chief investigator of the study, says, “Inhibiting sclerostin with romosozumab offers the opportunity to restore the bone regeneration balance. If successful, romosozumab could offer a significant breakthrough for reducing fractures in myeloma patients.”
The trial builds on studies undertaken in Professor Croucher’s laboratory showing that blocking sclerostin with an antibody increases bone formation and bone density in mouse models of myeloma. Now the researchers hope to demonstrate similar bone strengthening in patients to improve clinical outcomes.
“We hypothesise romosozumab can help reverse bone loss and repair lesions to reduce bone-related complications in myeloma. This is one of the first trials exploring this new therapeutic approach,” says Professor Tri Phan, co-investigator and Head of the IMAGE Lab at Garvan.
The pilot study will enrol patients with multiple myeloma who have damaged bones despite taking bone preservation therapy such as bisphosphonates or denosumab.
Participants will receive doses of romosozumab paired with vitamin D and calcium supplements, with their outcomes monitored for two years. The researchers will also apply single-cell sequencing techniques to examine romosozumab’s effects on the bone marrow microenvironment in unprecedented detail.
“These real-time insights can provide a blueprint for how the drug influences bone repair and cancer-bone interactions, to guide more effective use of romosozumab and its related therapies,” says Professor Phan.
“We hope this trial serves as a stepping stone toward improving survival and providing a better quality of life for myeloma patients affected by bone disease,” says Dr McCaughan.
Source: Garvan Institute