麻豆传媒

Belantamab mafodotin, a biologic agent targeting the B-cell maturation antigen (BCMA), elicited responses in about one-third of patients with relapsed or refractory multiple myeloma in the phase II y.

In this difficult-to-treat population of patients whose disease progressed after three or more lines of therapy, 31% of patients assigned to 2.5 mg/kg of belantamab mafodotin every 3 weeks had partial responses or better; this outcome was also achieved by 34% of patients receiving 3.4-mg/kg doses, reported Sagar Lonial, MD, of Emory University's Winship Cancer Institute, and colleagues.

The study was conducted at 58 centers in eight countries and included 293 patients who were refractory to immunomodulatory drugs and proteasome inhibitors, and refractory or intolerant to an anti-CD38 monoclonal antibody. The intention-to-treat population included 196 patients. The results were .

Very good partial response was achieved in 19% of patients assigned the 2.5-mg/kg dose and in 20% of patients assigned the 3.4-mg/kg dose.

Median duration of response has not yet been reached for either study group, but researchers estimated that more than 75% of patients will still be responding at 4 months or longer.

Median progression-free survival was 2.9 months in the 2.5- mg/kg group and 4.9 months in the 3.4-mg/kg group. Overall survival data were not yet mature.

"The IMiD/PI/anti-CD38 refractory patient population is a very difficult population to treat and there remains a critical need for the development of novel therapies," Sarah A. Holstein, MD, PhD, of the University of Nebraska Medical Center, told 麻豆传媒 in an email. "In the immediate future, there will be use of belantamab in the later lines of therapy; however, as anti-CD38 therapy moves more routinely to the front-line setting, it is likely that BCMA-directed therapy will move up to earlier lines of therapy."

Belantamab mafodotin is an immunoconjugate that combines a monoclonal antibody targeting the BCMA protein with monomethyl auristatin F, a microtubule disrupting compound. Lonial and colleagues explained that the drug, once bound to myeloma cells, kills them through several mechanisms.

Holstein noted that it is still unknown whether alternative means of targeting BCMA, such as with CAR T-cells, BiTEs, or bispecific antibodies, will be more efficacious and/or more readily accessible to patients compared with belantamab mafodotin.

Additionally, she said that although the 3-week cycle is quite feasible in the community, there are significant concerns regarding ocular toxicity associated with the agent.

"It was disappointing to learn that inclusion of steroid eye drops did not alter the occurrence of the ocular toxicity," Holstein said.

Indeed, keratopathy was the most common grade 3/4 adverse event in the safety analysis, occurring in 27% of the 2.5-mg/kg group and 21% of the 3.4-mg/kg group. In all, at least 70% of patients experienced some level of keratopathy or changes to corneal epithelium, and keratopathy was the most common reason for treatment discontinuation.

"Importantly, these patients regularly underwent ophthalmologic exam and the findings were used to make decisions about timing of dosing," Holstein said. "It will be difficult for all treated patients in the community to be co-managed by an ophthalmologist."

Holstein also noted that although the majority of keratopathy observed in the study did not lead to vision changes, there is still a concern that continued 3-week dosing without evaluation for corneal toxicity could lead to irreversible damage.

Other common grade 3/4 adverse events included thrombocytopenia and anemia. Two deaths were considered to be potentially related to treatment: one case of sepsis at the lower dose, and one case of hemophagocytic lymphohistiocytosis at the higher dose.

Comment