As reported at the 2024 ASCO Annual Meeting (Abstract LBA105) and in The New England Journal of Medicine by Meletios Dimopoulos, MD, and colleagues, an interim analysis from the phase III DREAMM-8 trial has shown significantly improved progression-free survival with belantamab mafodotin-blmf, pomalidomide, and dexamethasone (BPd) vs pomalidomide, bortezomib, and dexamethasone (PVd) in lenalidomide-exposed patients with relapsed or refractory multiple myeloma after at least one line of therapy.

Meletios Dimopoulos, MD

Study Details

In the open-label trial, 302 patients from sites in 18 countries were randomly assigned between October 2020 and December 2022 to receive BPd (n = 155) or PVd (n =147). Patients in the BPd group received 28-day cycles of belantamab ma­fodotin at 2.5 mg/kg on day 1 of cycle 1 and 1.9 mg/kg on day 1 of cycle 2 onward, plus pomalidomide and dexamethasone. The PVd group received 21-day cycles of bortezomib at 1.3 mg/m² on days 1, 4, 8, and 11 of cycles 1 through 8 and on days 1 and 8 of cycle 9 on­ward plus pomalidomide and dexa­methasone.

Overall, 53% of patients had received one previous line of therapy, and 14% had received four or more lines. Treatment continued until disease progression or unacceptable toxicity. The primary endpoint of the trial was progression-free survival per independent review committee assessment.

Progression-Free Survival

At data cutoff in January 2024 for the second interim analysis, median follow-up was 21.8 months (range = < 0.1–39.2 months). Progression-free survival rate at 12 months was 71% (95% confidence interval [CI] = 63%–78%) in the BPd group vs 51% (95% CI = 42%–60%) in the PVd group (hazard ratio [HR] = 0.52, 95% CI = 0.37–0.73, P < .001).

Partial response or better was observed in 77% of patients in the BPd group vs 72% of those in the PVd group, with complete response or better in 40% vs 16%, respectively. Complete response or better and undetectable measurable residual disease were achieved in 24% vs 5% of patients. Among patients who responded to treatment, response was ongoing at 12 months in 79% vs 61% of patients.

Overall survival data were immature at the time of analysis. Over­all survival rate at 12 months was 83% (95% CI = 76%–88%) in the BPd group and 76% (95% CI = 68%–82%) in the PVd group (HR = 0.77, 95% CI = 0.53–1.14).

Adverse Events

Grade ≥ 3 adverse events occurred in 94% of the BPd group vs 76% of the PVd group. The most commonly reported events in the BPd group included neutropenia (42%), thrombocytopenia (24%), blurred vision (17%), pneumonia (17%), and reduced visual acuity (13%); in the PVd group, the most commonly reported events were neutropenia (28%), thrombocytopenia (20%), and anemia (13%). Serious ad­verse events were reported in 63% vs 45% of patients. Adverse events led to discontinuation of any study treatment in 15% vs 12% of patients.

Overall, an ocular adverse event occurred in 89% of the BPd group (grade 3 or 4 in 43%) and 30% of the PVd group (grade 3 or 4 in 2%) and led to treatment discontinuation in 9% vs 0%. Ocular adverse events in the BPd group were managed with belantamab mafodotin dose modification.   

The investigators concluded: “Among lenalidomide-exposed patients with relapsed or refractory myeloma, BPd con­ferred a significantly greater benefit than PVd with respect to progression-free sur­vival, as well as deeper, more durable responses. Ocular events were common but were controllable by belantamab mafodotin dose modification.”

Dr. Dimopoulos, of the School of Medicine, National and Kapodistrian University of Athens, is the corresponding author of The New England Journal of Medicine article.

Disclosure: The study was funded by GSK. For full disclosures of the study authors, visit nejm.org.