Immunotherapy Combination Improves Overall Survival Rate in Patients with Advanced Melanoma

The addition of GM-CSF to ipilimumab treatment for patients with metastatic melanoma was found to decrease mortality risk by 35%, according to a study presented today at ASCO.

In a study of 245 patients with metastatic melanoma, adding growth factor GM-CSF to an increased dose of the immunotherapy ipilimumab (Yervoy) significantly improved survival over treatment with ipilimumab alone. The research, which was presented today at the 49th Annual Meeting of the American Society of Clinical Oncology (ASCO), provides evidence that combining immunomodulators may be an effective strategy to treat cancer.

The Phase II, proof-of-principle study enrolled patients who had received up to 1 prior treatment for metastatic melanoma. Subjects either received 10 mg/kg of ipilimumab alone or ipilimumab plus granulocyte-macrophage colony-stimulating factor (GM-CSF), a supportive cytokine therapy that works to boost white blood cell production. GM-CSF is commonly used in patients after chemotherapy or stem cell transplantation to ward off infection.

Approved by the FDA in 2011, ipilimumab works by blocking cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), a protein receptor typically found on the surface of T-cells. CTLA-4 downregulates the immune system, keeping T-cells inactive. By blocking this protein receptor, ipilimumab jump-starts the body’s immune response so that it can more efficiently fight tumors.

After 1 year of combination therapy, more than two-thirds (68.9%) of patients were alive, compared with half (52.9%) of those treated with ipilimumab alone. Although those in the combination arm had a 35% lower risk of mortality, the rates of tumor shrinkage (11% to 14%) were similar in both arms.

In addition, the combination therapy regimen appeared to decrease the incidence of some of the serious autoimmune-related side effects typically associated with ipilimumab treatment, which include endocrine deficiencies (gland or hormone), colitis, enterocolitis, vitiligo, hepatitis, dermatitis, lung toxicities, and neuropathy.

The researchers noted that the study is the first of its kind to look at the combination of ipilimumab and GM-CSF to fight cancer. They also noted they plan to conduct further clinical trials to assess the role of GM-CSF as an adjunct to other immune checkpoint targeting drugs.