An investigational drug with a novel mechanism of action has shown promise in the treatment of patients with relapsed/refractory multiple myeloma in a phase 2 trial. These patients had already been treated with a median of seven drugs, and yet the overall response rate was 30%.
The drug, belantamab mafodotin (GSK2857916, GlaxoSmithKline), is an immunoconjugate that targets B-cell maturation antigen (BCMA).
The new results come from the DREAMM-2 trial, which tested two doses of the drug in almost 200 patients.
The study was published online in the Lancet Oncology on December 16.
On the basis of these results, the company has submitted an approval application to the US Food and Drug Administration for use of belantamab mafodotin in the treatment of patients with relapsed or refractory multiple myeloma whose prior therapy includes an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody.
"Each day in my practice, I see patients who would benefit from additional therapeutic options because their disease has advanced and is no longer responding to available treatments," lead author Sagar Lonial, MD, Winship Cancer Institute of Emory University, Atlanta, Georgia, commented in a statement.
Describing BCMA as "one of the most promising targets in multiple myeloma research," Lonial said that the data "not only reinforce the significance of BCMA as a potentially viable target but also underscore the potential of belantamab mafodotin, if approved, as a practical treatment option in this patient population."
DREAMM-2 was an open-label, two-arm phase 2 study conducted at 58 specialty multiple myeloma centers in eight countries.
The investigators recruited adults with relapsed or refractory multiple myeloma who had experienced disease progression after undergoing at least three lines of therapy, whose condition was refractory to immunomodulatory drugs and proteasome inhibitors, and whose condition was refractory to or the patients were intolerant of an anti-CD38 monoclonal antibody.
These patients were randomly assigned in a 1:1 ratio to receive 2.5 mg/kg or 3.4 mg/kg intravenous belantamab mafodotin, given every 3 weeks on day one of each cycle, until disease progression or unacceptable toxicity. Patients received a median of three treatment cycles.
From 293 screened patients, 196 were included in the intention-to-treat population.
The team reports that 31% of patients in the lower-dose cohort and 34% in the higher-dose group achieved an overall response, as assessed by independent review. A very good partial response or better was seen in 19% and 20% of patients, respectively.
A clinical benefit, defined as a minimal response or better on independent review, was observed in 34% of lower-dose and in 39% of higher-dose patients.
The median duration of follow-up was 6.3 months and 6.9 months in the lower-dose and higher-dose groups, respectively. The probability of a duration of response of at least 4 months was 78% and 87%, respectively.
At the data cutoff, 58% of patients given the 2.5-mg/kg dose and 56% of those treated with the 3.4-mg/kg dose had experienced disease progression or had died.
The overall survival data were not mature at the time of data cutoff. The median progression-free survival was 2.9 months in the lower-dose group and 4.9 months in the higher-dose group.
At least one adverse event was recorded in 98% of lower-dose patients and in 100% of those in the higher-dose group; 54% and 62%, respectively, had adverse events that led to dose delays, and 29% and 41%, respectively, experienced adverse events that led to dose reductions.
The most common grade 3–4 adverse events were keratopathy, which occurred in 27% of lower-dose and in 21% of higher-dose patients, thrombocytopenia (20% and 33%), and anemia (20% and 25%).
Serious adverse events were reported in 40% of lower-dose and in 47% of higher-dose patients. The researchers note that two deaths, one from sepsis and one from hemophagocytic lymphohistiocytosis, were potentially related to treatment.
The manufacturer has planned a large phase 2 and 3 clinical program for belantamab mafodotin, with some studies already recruiting, including studies that will compare the drug to established therapies, either alone or in combination with other treatments.
The study was funded by GlaxoSmithKline. Lonial has received grant funding and personal fees from Celgene and Takeda and personal fees from Novartis, Bristol-Myers Squibb, GlaxoSmithKline, Amgen, Merck, and Janssen. Other authors have disclosed numerous relevant financial relationships, as listed in the original article.
Lancet Oncol. Published online December 16, 2019. Abstract
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Cite this: Belantamab Mafodotin Elicits Responses in R/R Multiple Myeloma - Medscape - Dec 23, 2019.