Prolonged Responses, Tolerability Seen With Monotherapy in Multiple Myeloma


Single-agent daratumumab conferred a favorable safety profile and exhibited evidence of durable responses in patients with heavily pretreated relapsed and refractory multiple myeloma, according to study results presented at the 59th American Society of Hematology Annual Meeting & Exposition (December 9-12, 2017; Atlanta, GA).

The monoclonal antibody daratumumab was granted accelerated approval by the Food and Drug Administration as a single-agent therapy for heavily pretreated multiple myeloma patients in November 2015. Several prior studies have shown the agent’s efficacy in this patient population.

Saad Z Usmani, MD, FACP, chief of plasma cell disorders at Levine Cancer Institute (Charlotte, NC), and colleagues reported long-term follow-up outcomes from 148 patients treated with single-agent daratumumab in the GEN501 and Sirius studies. All patients were relapsed and refractory following two or more prior treatments at the time of study entrance. Of the study populations, 76% had received three or more prior therapies, and 87% were refractory to both proteasome inhibitors and immunomodulatory drugs.

The studies had a median follow-up of 36.6 months (range, 0.5-42.3).

The most commonly observed treatment-related adverse events included fatigue (42%), nausea (30%), anemia (28%), back pain (27%), cough (26%), upper respiratory infections (22%), neutropenia (21%), thrombocytopenia (21%), pyrexia (20%), and nasal congestion (20%).

Grade 3 or higher adverse events seen in at least 5% of the study populations included anemia (18%), thrombocytopenia (14%), neutropenia (10%), and hypertension (5%). Forty-eight percent of patients experienced infusion-related adverse events, which largely occurred during the first infusion.

The study populations had an overall response rate of 30.4% (95% confidence interval [CI], 23.1-38.5). Twenty patients experienced a very good partial response or better, and seven patients experienced a complete response. Deep responses were sustained over time.


Related Content

Daratumumab Cost-Effective for Refractory Multiple Myeloma

FDA Approval Alert: Daratumumab Combination Approved for Multiple Myeloma


Among responding patients who remained progression free at 3 years, the median duration of response was 8 months (95% CI, 6.5-14.7), and the median overall survival (OS) among all patients was 20.5 months (95% CI, 16.6-28.1). The 3-year OS rate was 36.5% (95% CI, 28.4-44.6).

“Single-agent daratumumab continues to demonstrate a favorable safety profile with no new safety signals,” the researchers concluded. “With over one-third of our patients remaining alive after 3 years of study entry, these findings highlight the activity of single-agent daratumumab in this heavily pretreated population.”Cameron Kelsall