© ASCO/Todd Buchanan
CHICAGO—The anti-CD38 monoclonal antibody daratumumab can be effective as a stand-alone therapy for some heavily pretreated patients with multiple myeloma (MM), results of an ongoing phase 2 trial suggest.
The study, known as SIRIUS or MMY2002, included more than 100 patients who had received 3 or more prior lines of therapy.
Roughly 30% of these subjects responded to daratumumab, with a median response duration of about 7 months.
The median progression-free survival was close to 4 months, and the estimated 1-year overall survival rate was 65%.
Serious adverse events (AEs) occurred in 30% of patients.
“These findings speak to the potential of daratumumab as an effective and tolerable option for people with multiple myeloma who have exhausted other available treatment options,” said study investigator Sagar Lonial, MD, of Emory University School of Medicine in Atlanta, Georgia.
Dr Lonial presented these findings at the 2015 ASCO Annual Meeting (abstract LBA8512). The research was funded by Janssen Research & Development, the company developing daratumumab.
In part 1 of this study, 34 patients were randomized to receive either 8 mg/kg of daratumumab once every 4 weeks or 16 mg/kg once a week for 8 weeks, then once every 2 weeks for 16 weeks and once every 4 weeks after that, until disease progression or unacceptable toxicity.
In part 2, an additional 90 patients were enrolled to receive 16 mg/kg of daratumumab on the same dosing schedule as in part 1.
Dr Lonial reported results for all patients in parts 1 and 2 who received 16 mg/kg of daratumumab. These 106 patients had received a median of 5 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug.
According to an independent review committee, 29.2% of patients responded to daratumumab. Eighteen patients had a partial response, 10 had a very good partial response, and 3 had a stringent complete response. The median duration of response was 7.4 months.
“It is particularly noteworthy to see this level of response with a single-agent in this heavily pretreated population,” Dr Lonial said. “Ninety-seven percent of patients in this study were refractory to their last line of therapy, and 95% were double-refractory to both a [proteasome inhibitor] and an [immunomodulatory drug].”
The median overall survival has not been reached, and the estimated 1-year overall survival rate is 65%. The median progression-free survival was 3.7 months.
After a median follow up of 9.4 months, 45.2% of responders remain on therapy.
The most common AEs were fatigue (39.6%), anemia (33%), nausea (29.2%), thrombocytopenia (25.5%), neutropenia (22.6%), back pain (22.6%), and cough (20.8%).
Thirty percent of patients experienced serious AEs. And 4.7% of patients discontinued treatment due to AEs, none of which were considered drug-related.
Infusion-related reactions (IRR) were reported in 42.5% of patients and were predominantly grade 1 or 2 (4.7% grade 3; no grade 4). These occurred mainly during the first infusion.
The most common IRRs included nasal congestion (12%), throat irritation (7%), cough (6%), dyspnea (6%), chills (6%), and vomiting (6%)—all of which were treated with standard of care and slower infusion rates.
