A New Therapeutic Hope For Crippling Bone Cancer

The Garvan Institute of Medical Research has presented a novel therapeutic approach, which could profoundly decrease bone disease in those patients suffering from multiple myeloma, a type of bone cancer. Multiple myeloma develops in the bone and is the neoplastic proliferation of plasma cells (fully differentiated B lymphocytes capable of producing antibodies). It is the most common type of primary malignancy of the bone and can cause progressive destruction of bones resulting in increased risk for fractures and excruciating pain, frequently seen in ribs, spine and proximal long bones.  

Unlike the current therapeutic approaches, this new treatment will rebuild lost bone tissue, increasing its resistance towards fractures. This could significantly reduce the crippling pain of bone cancer.

Current Treatment For Multiple Myeloma?

Currently the medical treatment for multiple myeloma is upon diagnosis. Patients are treated with lenalidomide/ thalidomide (immunomodulatory agents; side effects: neutropenia, thrombocytopenia, venous thromboembolism and peripheral neuropathy) along with dexamethasone (corticosteroid). For poor prognosis multiple myeloma, bortezomib (proteasome inhibitor; side effects: peripheral and autonomic neuropathy) is highly effective and produces rapid responses.

After this initial therapy many patients under 80 years of age undergo autologous hematopoietic stem cell transplantation (patient’s own stem cells are used), which can prolong the duration of remission as well as over all survival. Allogeneic stem cell transplant (stem cells taken from donor) is potentially curative for multiple myeloma patients however its role in treatment is limited due to the unusually high (40-50%) treatment associated death rate in patients.

 The New Experimental Approach

The study published in the medical journal Blood, was presented in Brisbane this month, at an international meeting for experts of bone biology. The Australian research team specifically targeted a protein by the name of sclerostin. In healthy bones it regulates bone formation by arresting it. The researchers hypothesized that by inhibiting sclerostin’s activity they could potentially reverse the debilitating bone damage produced in multiple myeloma.

Though the current treatment regime can prevent further loss of bone, it by no means repairs the already damaged bones hence patients inevitably fracture. The new approach utilizes an antibody which neutralizes the protein sclerostin, thereby increasing bone mass and decreasing fracture incidence. In many of the tests a remarkable double the resistance to bone fractures was observed.

The treatment then proceeded to combine the antibody with a bisphosphonate drug (current standard treatment for myeloma). This combination of the anti-sclerostin antibody and zoledonic acid had a greater impact on increasing bone mass, strength and fracture resistance than the antibody treatment alone.

What Does This Mean?

Multiple myeloma while rare, has an extremely poor prognosis- less than 50% of those diagnosed survive for more than 5 years. Like other cancers, myelomas too vary with each individual. However targeting sclerostin, a protein actively functioning in everybody’s bones is not a target unique to an individual’s cancer. Hence there is great hope that in the future this treatment could be effective in at least most, if not all, multiple myeloma patients.

Citations

1. Michelle M. McDonald, Michaela R. Reagan, Scott E. Youlten, Sindhu T. Mohanty, Anja Seckinger, Rachael L. Terry, Jessica A. Pettitt, Marija K. Simic, Tegan L. Cheng, Alyson Morse, Lawrence M. T. Le, David Abi-Hanna, Ina Kramer, Carolyne Falank, Heather Fairfield, Irene M. Ghobrial, Paul A. Baldock, David G. Little, Michaela Kneissel, Karin Vanderkerken, J. H. Duncan Bassett, Graham R. Williams, Babatunde O. Oyajobi, Dirk Hose, Tri G. Phan, Peter I. Croucher. Inhibiting the osteocyte-specific protein sclerostin increases bone mass and fracture resistance in multiple myeloma. Blood, 2017; 129 (26): 3452 DOI: 10.1182/blood-2017-03-773341