In patients with multiple myeloma who were treated with at least three prior therapies (median five), daratumumab demonstrated substantial clinical activity and was well tolerated, investigators reported in the Lancet.
Overall response rates were observed in 31 of 106 people (ORR 29.2%; 95% confidence interval, 20.8-38.9), stringent complete responses in 3, and very good partial responses in 10 people. In total, 87 patients (82%) had received more than three lines of therapy: all patients had been treated previously with proteasome inhibitors and immunomodulatory drugs, and dexamethasone. In addition, 103 (97%) were refractory to the last line of therapy before study enrollment, and 95% were refractory to the most recent proteasome inhibitors and immunomodulatory drugs.
“Resistance to any previous therapy had no effect on the activity of daratumumab, lending support to a novel mechanism of action, but these findings need to be confirmed in larger studies,” wrote Dr. Sagar Lonial, executive vice chair of the department of hematology medical oncology, Emory University, Atlanta, and colleagues (Lancet. 2016 Jan 7. doi: 10.1016/S0140-6736[15]01120-4).
Daratumumab was well tolerated. The most common hematologic treatment-emergent adverse events of any grade were anemia (33%), thrombocytopenia (25%), and neutropenia (23%). The overall favorable safety profile makes it a promising candidate for combination regimens, and the monoclonal IgG1 antibody has shown early activity in combination with lenalidomide and dexamethasone, according to the researchers.
The open-label, multicenter, phase II trial included 106 patients who received daratumumab 16 mg/kg. The median time since initial diagnosis was 4.8 years (1.1-23.8 years), median number of previous therapies was 5 (2-14), and 80% of patients had received autologous stem cell transplantation.