Monotherapy with daratumumab demonstrated promising overall survival and objective response rates in patients with double-refractory multiple myeloma.
Saad Zafar Usmani, MD
Monotherapy with daratumumab, an anti-CD38 monoclonal antibody, demonstrated promising overall survival (OS) and objective response rates (ORR) in patients with double-refractory multiple myeloma, according to a single-arm phase II study presented at the 2015 ASCO Annual Meeting.
In the study, the 1-year OS rate was 65% and the ORR was 29.2% with daratumumab. In 2013, daratumumab received a breakthrough therapy designation as a treatment for patients with multiple myeloma. Under this program, Janssen, the company developing the drug, plans to submit data from the study to the FDA for potential approval.
“The efficacy we’re seeing is quite impressive for a clinical trial of refractory multiple myeloma, given that many patients had already undergone five or more types of treatment,” lead study author Saad Zafar Usmani, MD, a hematologist at Levine Cancer Institute/Carolinas Healthcare System, said in a statement. “Our hope is that daratumumab will help fill the unmet clinical need of patients who have exhausted available treatment approaches.”
In the pivotal phase II study, the first 34 patients enrolled received daratumumab at 16 mg/kg (n = 16) or 8 mg/kg (n = 18). After a response evaluation, the 16 mg/kg dose was selected for future study, with an additional 90 patients enrolled at this dose (N = 106).
Patients in the trial had received a median of five prior therapies over a median of 4.8 years following diagnosis. Ninety-six percent of patients were refractory to their last treatment, including proteasome inhibitors and immunomodulatory agents (95%).
Responses to daratumumab consisted of stringent complete responses (n = 3; 2.8%), very good partial responses (n = 10; 9.4%), and partial responses (n = 18; 17%). The median duration of response was 7.4 months, with a median time to progression of 3.7 months.
After a median follow-up of 9.4 months, the median OS had not been reached. At this analysis, 45.2% of patients remained on therapy.
Infusion-related reactions (IRR) predominately occurred during the first infusion and were mostly grade 1/2 (all-grade 42.5%). Grade 3 IRRs were seen in 4.7% of patients; however, no grade 4 events were experienced. No patients discontinued daratumumab as a result of an IRR.
The most common all-grade adverse events were fatigue (39.6%), anemia (33%), nausea (29.2%), thrombocytopenia (25.5%), back pain (22.6%), neutropenia (22.6%), and cough (20.8%). Overall, 4.7% of patients discontinued treatment due to adverse events. These side effects were not deemed to be associated with daratumumab.
“This is the first monoclonal antibody in myeloma that has shown single-agent activity. One in three patients in this study benefited from getting the drug, and that truly is unprecedented,” Usmani, said during a press briefing. “These results highlight the potential of daratumumab as a novel, well-tolerated, single-agent therapy in various stages of myeloma treatment.”
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.
“CD38 is highly expressed on multiple myeloma cells and is a promising therapeutic target,” Usmani noted.
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.
“Currently there are five big phase III studies that are evaluating daratumumab in combination with existing therapies. Three of the five are in the frontline setting,” explained Usmani.
Lonial S, Weiss BM, Usmani SZ, et al. Phase II study of daratumumab (DARA) monotherapy in patients with ≥ 3 lines of prior therapy or double refractory multiple myeloma (MM): 54767414MMY2002 (Sirius). J Clin Oncol. 2015;33 (suppl; abstr LBA8512).