For patients with multiple myeloma resistant to available therapies, an experimental drug displayed a 31 percent overall response rate and is thus a significant new option, leading oncologists report. The investigational agent, belantamab mafodotin, was tested in a phase II study led by Winship Cancer Institute of Emory University and conducted at 58 cancer centers in eight countries.
The results of the DREAMM-2 study (DRiving Excellence in Approaches to Multiple Myeloma) were published in Lancet Oncology. Sagar Lonial, MD, Winship chief medical officer, chair of the Emory Department of Hematology and Medical Oncology, and principal investigator on the study, says this is a significant development for patients who are resistant to the three main classes of drugs used to treat myeloma, a cancer caused by malignant plasma cells that accumulate in the bone marrow.
"We clearly saw activity in patients with relapsed and refractory myeloma by using something that was new and different to their treatment paradigm. That concept of bringing in a new target into the treatment of refractory myeloma with about a third of patients responding, is a really a big step forward for patients," said Lonial.
The DREAMM-2 study found that belantamab mafodotin has a manageable safety profile with no new safety concerns compared with the DREAMM-1 trial. Patients in the trial had actively progressing multiple myeloma that had worsened despite three or more lines of therapy with immunomodulatory-based drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies. Overall, patients in DREAMM-2 had more advanced disease, poorer prognosis and performance status, and also had a greater number of prior lines of therapy in comparison with patients in DREAMM-1. The study was sponsored by GlaxoSmithKline (GSK), which manufactures belantamab mafodotin.
Patients were randomly assigned to either receive 2.5mg/kg or 3.4mg/kg of belantamab mafodoton. Myeloma levels decreased in thirty of the 97 patients (31 percent) in the 2.5 mg/kg cohort, thereby achieving an overall response, and 60 percent of those responders achieved a 90 percent or more reduction in myeloma levels, considered a very good partial response or better. Based on that data, GSK is moving forward with a U.S. Food & Drug Administration submission seeking approval of the 2.5 mg/kg dose administered every three weeks.
"From a patient perspective, I think DREAMM 2 offers hope. When you're in a situation where you don't have a lot of treatment options or the treatment options can be quite toxic with very short-lived remissions, belantamab mafodotin offers something that can be quite impressive," says Lonial.
Belantamab mafodotin is a humanized, immunoconjugate that targets B-cell maturation antigen (BCMA), a protein on the surface of almost all plasma cells that is an important part of cell resistance and proliferation signals that help myeloma cells survive. According to the study, BCMA expression is an ideal therapeutic target because it is almost exclusively limited to plasma cells, resulting in fewer off-target effects resulting from the therapy.
"While we've made huge strides in improving outcomes for patients, there certainly are patients who have exhausted available treatment options, and so for those patients, new treatment options or targets are really necessary," according to Lonial.
A Phase III study is currently testing belantamab mafodotin as third-line monotherapy for relapsed/refractory multiple myeloma, and in combination with standard and novel treatments.