Richard Pazdur, MD
Acting 4 months ahead of schedule, the FDA has granted an accelerated approval to the CD38-targeted monoclonal antibody daratumumab (Darzalex) as a monotherapy for patients with multiple myeloma following at least 3 prior therapies, based on data from two open-label clinical trials.
“The responses we saw in clinical trials that led to today’s approval were striking, especially considering that these patients received a median of five prior lines of therapy,” Sagar Lonial, MD, chief medical officer, Winship Cancer Institute of Emory University and Professor and Executive Vice Chair, Department of Hematology and Medical Oncology, Emory University School of Medicine, said in a statement. “It appears the mechanism of action for daratumumab may play an important role in its single-agent activity among this group of advanced-stage multiple myeloma patients.”
Daratumumab is a fully human monoclonal antibody that binds to glycoprotein CD38. Once bound, the antibody interacts with natural killer cells by mimicking the normal interaction between CD38 and CD31. This interaction elicits antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity resulting in antitumor activity.
A full indication for daratumumab is contingent on confirmatory studies, which are currently ongoing. The indication for daratumumab is specifically for patients following progression on a proteasome inhibitor and an IMiD or for those who are double refractory to a proteasome inhibitor and IMiD.
“Multiple myeloma is a highly complex disease and remains incurable, with almost all patients relapsing or becoming resistant to therapy,” Paul G. Richardson, MD, clinical program leader and director of Clinical Research, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, said in a statement. “With Darzalex, we have a promising new immunotherapy, which has shown pronounced efficacy as a single agent with an acceptable adverse event profile. This is especially important for treating these heavily pre-treated patients in whom all of the major classes of currently available medicines have failed.”
In addition to single-agent activity, daratumumab is also being explored in a number of combination studies. At this time, several phase III clinical trials are looking at the antibody in various treatment settings.Â
Lonial S, Weiss BM, Usmani SZ, et al. Phase II study of daratumumab (DARA) monotherapy in patients with â‰¥ 3 lines of prior therapy or double refractory multiple myeloma (MM): 54767414MMY2002 (Sirius). J Clin Oncol. 2015;33 (suppl; abstr LBA8512).
Lokhorst HM, Plesner T, Laubach JP, et al. Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma [published online August 26, 2015]. N Engl J Med. doi: 10.1056/NEJMoa1506348