Drugs known as monoclonal antibodies, engineered to target disease-harbouring proteins on the surface of cells or to block growth signals in the microenvironment, have demonstrated strong efficacy and safety, and have become more common treatments for blood cancers.

Given this success, researchers are experimenting with the use of monoclonal antibodies in rare diseases with limited treatment options.

One such disease is multicentric Castleman’s disease (MCD), a potentially fatal, incurable disorder with high morbidity believed to be partially mediated by the overproduction of a specific cell signaling molecule known as interleukin-6 (IL-6) that results in the dangerous overgrowth of cells in the lymph nodes.

This study evaluated the safety and efficacy of siltuximab, an investigational monoclonal antibody designed to block the function of IL-6 in an attempt to ameliorate uncontrolled cell growth and control other inflammatory disease symptoms.

Investigators enrolled 79 MCD patients in a Phase II trial who were randomized to receive either siltuximab or placebo, in combination with best supportive care, to assess rates of remission and improvement in symptoms.

Roughly one-third of patients treated with siltuximab achieved a durable tumor and symptom response whereas none of the placebo-treated patients showed a response.

While disease symptoms completely resolved in one-quarter of the siltuximab-treated patients for a median of 1.3 years, this was never observed in patients treated with placebo, indicating that siltuximab led to prolonged duration of disease control. Rates of adverse events were similar between the treatment and placebo groups, despite a two-fold longer duration of treatment in the siltuximab group.

“Based on these promising results, it appears that patients treated with this highly targeted monoclonal antibody approach can potentially experience far superior and equally safe responses than those observed with current conventional treatments,” said study author Raymond S. Wong, MBChB, MD, of the Prince of Wales Hospital and the Chinese University of Hong Kong. “If siltuximab gains regulatory approval, this experimental therapy could become the first globally approved treatment for this incurable disease and could potentially transform how patients are treated in the future.”

Source: ASH