Treatment with the combination of daratumumab plus pomalidomide/dexamethasone resulted in rapid, deep, and sustained responses with no new safety signals in patients with heavily treated multiple myeloma.
Treatment with the combination of daratumumab plus pomalidomide/dexamethasone resulted in rapid, deep, and sustained responses with no new safety signals in patients with heavily treated multiple myeloma, according to a recent study.
“The findings from this clinical study complement the results of the POLLUX phase III study, in which a combination of daratumumab with lenalidomide/dexamethasone induced a high overall response rate and significantly reduced the risk for disease progression and death in patients with relapsed or refractory multiple myeloma compared to lenalidomide/dexamethasone,” wrote Ajai Chari, MD, of Tisch Cancer Institute, Mount Sinai School of Medicine, New York, and colleagues in a study published in Blood. “In the present study, addition of daratumumab to another immunomodulatory drug, pomalidomide, resulted in deep and durable responses, including minimal residual disease (MRD) negativity, in heavily treated patients with relapsed or refractory disease.”
The study included 103 patients with relapsed or refractory myeloma treated with at least two prior lines of therapy; more than three-quarters of patients had received three or more prior therapies. Patients were given daratumumab 16 mg/kg, pomalidomide 4 mg daily for 21 days of each 28-day cycle, and dexamethasone 40 mg weekly. The median age of patients was 64.
The primary endpoint of the study was safety. In all, 67% of patients discontinued treatment either due to progressive disease (39%); adverse events (16%); or physician’s decision, withdrawal of consent, or death (4% each).
According to the researchers, the safety profile of the three-drug combination was similar to that seen with pomalidomide/dexamethasone alone; however, one-half of patients experienced daratumumab-specific infusion-related reactions. In addition, there was a higher rate of neutropenia (77%), but the researchers noted that the rates of grade 3/4 infection (32%) and febrile neutropenia (7%) were comparable to the safety profile of pomalidomide/dexamethasone alone.
Other common grade 3 or worse adverse events were anemia (28%), leukopenia (24%), thrombocytopenia (19%), lymphopenia (14%), and fatigue (12%). Serious treatment-related adverse events occurred in 53% of patients; 18% of those were deemed to be related to daratumumab.
The overall response rate was 60%. Eight percent of patients achieved stringent complete response and 9% achieved complete response. The clinical benefit rate was 62%. Response was consistent throughout all subgroups tested, including patients with double-refractory disease (ORR, 58%).
Among the 62 patients with a response, the median duration of response was not estimable. Among those with a complete response or better, almost one-third (29%) were MRD negative.
“In our study, the depth of response reached in heavily treated patients was remarkable, with 42% of patients achieving a very good partial response or better and some patients becoming free of MRD,” the researchers noted.
With a median follow-up of 13.1 months, the median progression-free survival was 8.8 months and the median overall survival was 17.5 months. Patients with standard cytogenetic risk had a median progression-free survival of 10.3 months and those with high-risk disease had a median of 3.9 months.
“Further evaluation of daratumumab plus pomalidomide/dexamethasone is underway in the ongoing APOLLO study conducted by the European Myeloma Network,” the researchers wrote.