The addition of the anti-CD38 antibody daratumumab to traditional backbone therapies used in the treatment of multiple myeloma was well tolerated and associated with high rates of responses, according to the results of a phase Ib study presented at the 2014 ASH Annual Meeting.
Maria-Victoria Mateos, MD, PhD, presented the results of the study during a press conference.
Daratumumab belongs to a new class of drugs, anti-CD38 antibodies, which target multiple myeloma by binding to CD38 expressed on the myeloma cell and signaling to the patient’s immune cells to attack the myeloma cells. To date, daratumumab has shown efficacy as a single-agent in patients with relapsed or refractory myeloma with a manageable safety profile.
Mateos and colleagues were interested in testing the safety and tolerability of daratumumab in combination with several already established treatment regimens to see if response rates could be improved with the combinations. In this phase Ib study, they assigned 17 patients to 16 mg/kg daratumumab and one of the following four regimens:
• Bortezomib/dexamethasone (VD)
• Bortezomib-thalidomide/dexamethasone (VTD)
• Bortezomib/melphalan/prednisone (VMP)
• Pomalidomide/dexamethasone (POM-D).
The median age of patients assigned to each arm varied from 57 years for those on daratumumab plus VTD to 72.5 years for daratumumab plus VD. Patients were able to complete a median of 9 infusions in the VD arm; 12.5 in the VMP arm; 8 in the VTD arm; and 11 in the POM-D arm.
According to Mateos, the safety profile differed for each backbone therapy used. Serious side effects including pneumonia, soft-tissue infection, and pre-renal failure occurred in patients assigned daratumumab plus VD. Infection also occurred in patients assigned daratumumab plus POM-D. No serious side effects occurred in the VMP and VTD arms. Mateos noted that most of these serious side effects were related to the backbone therapy. Only one adverse event related to daratumumab occurred and four patients experienced infusion-related reactions associated with daratumumab; however, this did not interrupt treatment.
Looking at the efficacy of the combination regimens, results showed that 50% of patients assigned to daratumumab plus POM-D responded to treatment and one patient achieved complete remission. In the three other arms, all patients achieved partial or very good partial responses.
“Median time to first response was rapid in all arms,” Mateos said. “This is consistent with what we have previously observed with these backbone treatments.”