DREAMM-8 Trial Demonstrates Benefits of Belantamab Mafodotin

Meletios Dimopoulous, MD

Belantamab mafodotin-blmf (Blenrep) in addition to pomalidomide (Pomalyst) and dexamethasone (BPd) was generally well tolerated compared with bortezomib (Velcade) plus pomalidomide and dexamethasone (PVd) in patients with pretreated, relapsed/refractory multiple myeloma. Further, health-related quality of life (HR-QOL) was maintained over time, according to patient-reported outcome (PRO) data from the phase 3 DREAMM-8 trial (NCT04484623).¹

Results presented during the 21st International Myeloma Society Annual Meeting did not reveal significant differences in global health status and QOL (GHS/QOL) scores between patients in the BPd (n = 133) and VPd arms (n = 124) from week 5 to 137, as measured by the European Organisation for Research and Treatment of Cancer (EORTC): Quality of Life Questionnaire-Core Module 30 (QLQ-C30). Furthermore, domain scores for role and physical functioning, fatigue, and disease symptoms/pain were comparable across treatment arms.

However, a higher proportion of patients achieved meaningful improvements (≥10 points) in EORTC scores at any time point with BPd vs PVd. The most notable differences were observed for physical functioning (53.6% vs 31.3%) and fatigue (65.2% vs 46.3%), respectively. Differences were also seen in the GHS/QOL (49.0% vs 39.5%), role functioning (51.6% vs 39.5%), and disease symptom (56.8% vs 43.5%) domains.

“Overall, in combination with the significant progression-free survival [PFS] benefit [generated] with BPd vs PVd, [as] observed in DREAMM-8, these results further support the use of BPd as a potential new standard of care in patients with relapsed/refractory multiple myeloma,” presenting author Meletios A. Dimopoulos, MD, professor and chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine in Greece, stated.

Findings from DREAMM-8 were previously reported at the 2024 ASCO Annual Meeting and showed a statistically significant PFS benefit with BPd vs PVd, meeting the trial’s primary end point. The median PFS was not reached (NR; 95% CI, 20.6-NR) with BPd vs 12.7 months (95% CI, 9.1-18.5) with PVd (HR, 0.52; 95% CI, 0.37-0.73; P < .001). Moreover, BPd reduced the risk of disease progression or death across all prespecified subgroups, including in patients with cytogenetic high-risk disease, with lenalidomide (Revlimid)–refractory disease, and who received prior treatment with anti-CD38 therapy.² Further, the PFS rates at 12 months were 71% with BPd and 51% with PVd.¹

Study Overview

DREAMM-8 enrolled patients with multiple myeloma who received at least 1 prior line of therapy including lenalidomide and had documented disease progression during or following their most recent treatment. Patients could not have had prior exposure to an anti-BCMA agent or pomalidomide and were not enrolled if they were refractory or intolerant to bortezomib. Key stratification factors included prior treatment lines, prior exposure to bortezomib, and prior exposure to anti-CD38 therapy.¹

Microscopic, photorealistic image of myeloma cells - Generated with Adobe Firefly

Patients were enrolled onto the study between October 2020 to December 2022, and 155 and 147 were randomly assigned 1:1 to the BPd arm or PVd arm, respectively. In the BPd arm, patients received 2.5 mg/kg of intravenous belantamab mafodotin during cycle 1, followed by 1.9 mg/kg every 4 weeks from cycle 2 onward; 4 mg of oral pomalidomide on days 1 to 21; and 40 mg of dexamethasone on days 1, 8, 15, and 22. Treatment in the comparator arm comprised 1.3 mg/m2 of subcutaneous bortezomib on days 1, 4, 8, and 11 of cycles 1 to 8, followed by days 1 and 8 of each subsequent cycle; 4 mg of pomalidomide on days 1 to 14; and 20 mg of dexamethasone on the day of and day after treatment with bortezomib. Treatment continued until disease progression, death, unacceptable toxicity, withdrawal of consent or study cessation.

The trial’s primary end point was PFS by independent review committee assessment according to the International Myeloma Working Group criteria. Secondary end points included overall survival, minimal residual disease negativity, duration of response, overall response rate, complete response rate, very good partial response or greater, time to best response, time to progression, PFS2, adverse effects (AEs), ocular findings, and PROs.

PRO assessments included the EORTC QLQ-C30 instrument, which evaluated GHO/QOL, physical functioning, role functioning, and fatigue; the EORTC QLQ-Multiple Myeloma Questionnaire (EORTC QLQ-MY20), which evaluated symptom domain; the Functional Assessment of Cancer therapy–General Population (FACT-GP5) test which evaluated the overall impact of bothersome adverse effects (AEs); the PRO-CTCAE which evaluated symptomatic toxicities; and the ocular surface disease index (OSDI), which assessed vision-related functioning. High scores on the EORTC QLQ-C30 test indicated better QOL, better physical or role functioning, and worse fatigue. Higher scores on all other measures indicated worsened functioning, wellbeing, or toxicities.

The EORTC QLQ-C30 and EORTC QLQ-MY20 instruments were used in the intention-to-treat population; PRO-CTCAE, FACT-GP5, and OSDI tests were analyzed in the safety population. All PRO assessments were performed at baseline and every 4 weeks during treatment, except the OSDI, which was performed every 8 weeks after week 31 and then less frequently. During treatment, the adherence to PRO assessment was greater than 90% for most visits up to week 53.

Baseline characteristics were well-balanced between treatment arms. The median age of patients was 67 years (range, 40-82) in the BPd arm and 68 years (range, 34-86) in the PVd arm. The majority of patients across both arms were male (64% vs 56%), White (86% vs 87%), had an ECOG performance score of 1 or less (97% vs 97%), and had stage I/II disease at screening (60% vs 58%). Regarding cytogenetic abnormalities, patients had standard-risk cytogenetics (46% vs 51%), high-risk cytogenetics (34% vs 32%), and missing or nonevaluable abnormalities (20% vs 17%), respectively, and most patients experienced relapse more than 12 months after initiating first-line treatment (86% vs 86%). The median time since diagnosis was 4.04 years (range, 0.4-16.7) in the BPd arm and 3.43 years (range, 0.4-17.7) in the PVd arm. Extramedullary disease was present in 13% and 7% of patients in these respective arms.

Additional Data on Treatment Toxicities

Over 53% of patients with available data across both arms reported no to low severity, interference or frequency of symptomatic AEs at all visits, with a maximum PRO-CTCAE score of less than 3 post-baseline. Ocular toxicities were generally manageable with dose modification and had a minimal impact on PRO QOL. Moreover, the incidence of treatment discontinuation due to ocular toxicities was low, which is consistent with previously reported data.

Additionally, worsening of vision-related function was reported in a higher proportion of patients treated with BPd (73%) vs PVd (51%), per OSDI scores. However, most of these patients later reported improvements in vision-related functions; in the BPd arm (n = 110), 92% of patients experienced an improvement in vision-related function after a median of 57 days.

According to FACT-GP5 scores, most patients in both treatment arms reported low levels of bother from treatment-related AEs. At week 49, approximately 17% of patients in the BPd arm reported being “quite a bit” or “very much” bothered by these AEs.

Disclosures: Dr Dimopoulos reported receiving honoraria from participation in advisory boards and satellite symposia from Amgen, Sanofi, Regeneron, Menarini, Takeda, GSK, Bristol-Myers Squibb, Janssen, BeiGene, Swixx, and AstraZeneca.

REFERENCES:

1. Dimopoulos M, Becksac M, Pour L, et al. Belantamab mafodotin, pomalidomide, and dexamethasone vs pomalidomide, bortezomib, and dexamethasone in patients with relapsed/refractory multiple myeloma: patient-reported outcomes from DREAMM-8. Presented at: 2024 International Myeloma Society Annual Meeting; September 25-28, 2024; Rio De Janeiro, Brazil. Abstract OA-13.

2. Trudel S, Beksac M, Pour L, et al. Results from the randomized phase 3 DREAMM-8 study of belantamab mafodotin plus pomalidomide and dexamethasone (BPd) vs pomalidomide plus bortezomib and dexamethasone (PVd) in relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2024;(suppl 17):LBA105.