“Taken together with results from the [previous] DREAMM-7 trial, these data highlight the potential of belantamab mafodotin-containing triplets to address an unmet need for novel regimens to treat patients with multiple myeloma at the first relapse,” senior author Suzanne Trudel, MD, of the department of medical oncology and hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada, said in presenting the late-breaking findings in a press briefing at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.
The results, published concurrently in The New England Journal of Medicine, are from an interim analysis of the ongoing phase 3, global open-label DREAMM-8 trial, involving 302 patients with lenalidomide-refractory multiple myeloma who were randomized to treatment with either belantamab mafodotin (n = 155) or bortezomib (n=147), each in addition to the pom-dex combination.
The study met its primary endpoint of PFS at a median follow-up of 21.8 months, with the median PFS in the belantamab mafodotin group not met, and the rate 12.7 months for bortezomib (HR 0.52; P < .001).
The 12-month rate of PFS was significantly higher with belantamab mafodotin compared with the bortezomib group (71% versus 51%).
The overall response rates between the 2 groups were similar (77% versus 72%), however, the belantamab mafodotin group had an improved rate of complete response of 40% versus 16% in the bortezomib group.
The median duration of response was not reached with belantamab mafodotin versus 17.5 months with bortezomib.
While a positive trend for median overall survival favored belantamab mafodotin for median overall survival (HR .77), the authors note that survival data still need to mature.
Further analyses showed early and sustained separation in favor of belantamab mafodotin for PFS in all prespecified subgroups, including those with high-risk cytogenetics, and those refractory to lenalidomide and anti-CD38s.
In terms of safety, grade 3 or higher adverse events (AEs) occurred among 91% of those in the belantamab mafodotin group compared with 73% in the bortezomib group, however, when the researchers adjusted for time on treatment, the belantamab mafodotin group had similar or lower rates of AEs.
Discontinuation rates for fatal or AEs of any cause were similar in both arms.
The most prominent side effects of belantamab mafodotin are the ocular AEs that affect the majority of patients. In the DREAMM-8 study, the ocular events affected 89% of patients, with events that were grade 3 or higher occurring among 43% (grade 3, 42%; grade 4, 1%).
The ocular events, which included blurred vision, dry eye, and a foreign body sensation in the eyes, were generally reversible and managed with treatment delays and dose modifications.
As of the time of the analysis, the first occurrence of the ocular events had improved in 92% of patients and resolved in 85%, with a median time to resolution of 57 days.
The AEs resulted in treatment discontinuation for 9% of patients.
The ocular events were managed with a protocol-recommended modification of the belantamab mafodotin dose, which included dose delays until the KVA grade improved to 1 or lower, as well as reductions in the frequency of administration from every 4 weeks to every 8 weeks.
“Ocular AEs are seen in the majority of patients, and the best strategies to mitigate things at this time that we know of are dose holds for grade 2 ocular events, which allow for full recovery and minimize cumulative toxicity, and then prolonging dosing intervals for subsequent doses,” Dr. Trudel said in an interview.