Multiple myeloma is one of the most common hematologic cancers, second only to the non-Hodgkin lymphomas. Yet it remains incurable and efforts to develop targeted monoclonal antibody (mAb) achieved clinical benefits years after their development for other malignancies.1-4
“Daratumumab was definitely a game-changer,” said Sandy Wong, MD, an assistant professor at the University of California, San Francisco School of Medicine. “It’s had a profound impact. It’s really and truly changed how we treat in the relapsed/refractory setting.”
Daratumumab targets cell-surface CD38, which is “highly and uniformly” expressed on more than 97% of myeloma cells, Dr Wong noted.1
“Monoclonal antibody work has been going on for many years and there have been a lot of setbacks along the way,” Dr Wong told Cancer Therapy Advisor.
“I honestly don’t think anybody really knows why exactly daratumumab and elotuzumab — the 2 U.S. Food and Drug Administration-approved onco-antibodies for multiple myeloma — worked out,” she said. “There have been a lot of other anti-CD38 antibodies developed in the past and most didn’t make it.”
Daratumumab’s complement-dependent cytotoxicity (CDC) was recognized early on as one mechanism of action against myeloma cells, but, over time, other properties have been recognized, Dr Wong noted.
“More and more, it has exhibited antibody-dependent cell-mediated cytotoxicity [ADCC] and antibody-dependent cellular phagocytosis (ADCP),” she explained. “More recently, it’s thought to influence the immune response in the patient’s body. We are learning more and more of the story over time.”
The antigen epitope might be responsible for daratumumab’s antimyeloma activity because of how it interacts with patients’ immune system, Dr Wong speculated.
“It may very well be that somehow something about this particular epitope over time changes the immune environment of the patient,” she explained. “But that’s a hypothesis. I don’t think anybody knows for sure.”