In the phase II DREAMM-2 trial reported in The Lancet Oncology, Sagar Lonial, MD, and colleagues found that the antibody-drug conjugate belantamab mafodotin was active in patients with heavily pretreated relapsed or refractory multiple myeloma. The agent is a conjugate of an anti–B-cell maturation antigen antibody and the microtubule-disrupting agent monomethyl auristatin F.
Sagar Lonial, MD
In the open-label trial, 196 patients from 58 sites in eight countries were randomly assigned between June 2018 and January 2019 to receive belantamab mafodotin at 2.5 mg/kg (n = 97) or 3.4 mg/kg (n = 99) via intravenous infusion every 3 weeks until disease progression or unacceptable toxicity. Patients had to have disease progression after three or more lines of therapy, were refractory to immunomodulatory drugs and proteasome inhibitors, and refractory or intolerant to an anti-CD38 monoclonal antibody. Patients had received a median of six to seven prior lines of therapy, with 83% to 84% having received more than four lines.
As of the primary analysis data cutoff date in June 2019, objective response as assessed by independent review committee had occurred in 30 patients in the 2.5-mg/kg group (31%, 97.5% confidence interval [CI] = 20.8%–42.6%) and 34 patients in the 3.4-mg/kg group (34%, 97.5% CI = 23.9%–46.0%). At median durations of follow-up of 6.3 and 6.9 months, median duration of response was not reached in either group. Median progression-free survival was 2.9 months and 4.9 months.
The most common grade 3 or 4 adverse events in both the 2.5-mg/kg and 3.4-mg/kg groups were keratopathy (27% and 21%), thrombocytopenia (20% and 33%), and anemia (20% and 25%). Serious adverse events were reported in 40% and 47% of patients. Treatment was discontinued due to adverse events in 8% and 10%, with keratopathy being the most common cause. Two deaths were considered potentially related to treatment—one due to sepsis in a patient in the 2.5-mg/kg group, and one due to hemophagocytic lymphohistiocytosis in a patient in the 34-mg/kg group.
The investigators concluded, “Single-agent belantamab mafodotin shows antimyeloma activity with a manageable safety profile in patients with relapsed or refractory multiple myeloma.”
Dr. Lonial, of the Winship Cancer Institute of Emory University, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by GlaxoSmithKline. For full disclosures of the study authors, visit thelancet.com.