Belantamab Mafodotin Elicits Deep, Durable Responses in Heavily Pretreated Relapsed/Refractory Myeloma

Sagar Lonial, MD

The antibody-drug conjugate belantamab mafodotin (belamaf; Blenrep) continued to showcase efficacy and tolerability in heavily pretreated patients with relapsed/refractory multiple myeloma, inducing durable responses even in those who had previously received 7 or more lines of therapy, according to data from a post-hoc analysis of the DREAMM-2 trial (NCT03525678) presented during the 2020 ASH Annual Meeting & Exposition.

In the study, investigators examined the safety and efficacy of single-agent belamaf, a first-in-class antibody-drug conjugate that targets the B-cell maturation antigen (BCMA). Two subpopulations of patients were treated with the recommended dose of 2.5 mg/kg every 3 weeks: patients treated with 3 to 6 (n = 47), and ≥7 therapies (n = 50) prior to entry in DREAMM-2.

The pivotal DREAMM-2 study showed that single-agent belamaf induces deep and durable clinical activity and has a manageable safety profile with up to 13 months of follow-up in heavily pretreated relapsed/ refractory patients with multiple myeloma. The ongoing open-label study evaluated treatment at 2.5 mg/kg or 3.4 mg/kg administered intravenously every 3 weeks in patients with at least 3 prior lines of therapy who were refractory to an immunomodulatory drug and a proteasome inhibitor and/or intolerant of an anti-CD38 monoclonal antibody.

Patients with multiple myeloma typically become refractory to successive types of therapy. Furthermore, the depth of response decreases and remissions shorten as the number of therapy lines increase. Therefore, new effective treatments are urgently needed for these patients, lead author Sagar Lonial, MD, professor and chair in the Department of Hematology and Medical Oncology and the Anne and Bernard Gray Family Chair in Cancer at Emory University School of Medicine in Atlanta, Georgia, said during his presentation.

The primary end point was overall response rate. Patients underwent regular ocular exams by an eye care professional to fully characterize ocular events. Keratopathy (damage to the cornea due to dryness caused by incomplete or inadequate eyelid closure resulting in loss or insufficiency of the tear film) and visual acuity were evaluated using the Keratopathy and Visual Acuity (KVA) scale, as well as changes in best corrected visual acuity.

The median age of patients in the 3 to 6 and ≥7 prior therapies groups was 62 (range, 39–85) and 67 (range, 45–85) years, respectively. “Body mass index, ethnicity, International Staging System grade, and high-risk genetic background were well matched between the [3 to 6 and ≥7 prior treatment groups],” said Lonial, who is also chief medical officer at Winship Cancer Institute of Emory University.

“All patients across both groups were triple refractory, that is, refractory to at least 1 therapy from each of the immunomodulatory, proteasome inhibitor, and monoclonal antibody drug classes of therapy,” Lonial said.

Overall survival was 13.7 months in patients with 3 to 6 prior line of therapy and 13.4 months in patients with ≥7 prior lines of therapy. Progression-free survival rates were slightly better for the less heavily pretreated patients, said Lonial, at 2.9 months versus 2.2 months.

The objective response rate was 34% and 30% in patients with 3 to 6 and ≥7 prior therapies, respectively. In the 3 to 6 prior therapies group, 17% had at least a very good partial response (VGPR) and in the ≥7 prior therapies group, 20% had VGPR or better. Response was durable in both groups, with investigators reporting a duration of response of 11.0 months in the 3 to 6 prior therapy group and 13.1 months in the ≥7 prior therapy group.

The safety profile of belamaf was similar in both groups with comparable rates of adverse events (AEs), serious AEs, and dose modifications, and comparably low rates of treatment discontinuation. The most common AEs were largely similar across the 2 subgroups, including ocular events as anticipated with monomethyl auristatin F (MMAF)–containing antibody-drug conjugates.

The most common grade 3/4 adverse events (>10% in the 3 to 6 or ≥7 prior therapies groups) were keratopathy (3 to 6, 33%; ≥7, 27%), thrombocytopenia (3 to 6, 17%; ≥7, 20%), anemia (3 to 6, 11%; ≥7, 31%), and decreased lymphocyte count (3 to 6, 11%; ≥7, 14%). Lonial noted that the rate of anemia was higher in the more heavily pretreated group.

Across both subgroups, AEs were managed with dose delays (3 to 6, 59%; ≥7, 49%) and reductions (3 to 6, 37%; ≥7, 33%); discontinuations due to treatment-related AEs were uncommon (3 to 6, 7%; ≥7, 8%).

Rates of corneal events that were graded by investigators according to the KVA scale were very similar between the 2 groups.

“This post hoc analysis showed that the efficacy and safety was not affected by the number of prior therapies,” said Lonial. “Belamaf achieved deep and durable responses, with no notable alterations in its safety profile, even when patients have received 7 or more prior lines of therapy,” he concluded.

Belamaf is approved for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 4 prior therapies based on prior results of the DREAMM-2 study.

Reference

1. Lonial S, Lee HC, Badros AZ, et al. DREAMM-2: single-agent belantamab mafodotin (Belamaf) in patients with relapsed/refractory multiple myeloma (RRMM) – 1-year outcomes by prior therapies. Presented at: 2020 ASH Annual Meeting; December 5-8, 2020; Virtual. Abstract 1417.