Belamaf plus pomalidomide/dexamethasone improves PFS in relapsed/refractory multiple myeloma

In patients with relapsed/refractory multiple myeloma (RRMM) who received at least one prior line of therapy (LOT), treatment with belantamab mafodotin (belamaf) plus pomalidomide and dexamethasone (BPD) results in statistically significant and clinically meaningful progressive-free survival (PFS) compared with pomalidomide plus bortezomib and dexamethasone (PVD), as shown in the DREAMM-8 study.

“BPD also led to deeper and more durable responses, showed a favourable overall survival (OS) trend, and had a manageable safety profile,” said Dr Meletios A Dimopoulos, School of Medicine, National and Kapodistrian University of Athens, Department of Clinical Therapeutics, Athens, Greece.

DREAMM-8 is a phase III, open-label, randomized, multicentre trial that assessed the safety and efficacy of BPD versus PVD in RRMM patients previously treated with lenalidomide.

Dimopoulos and his team randomized eligible participants 1:1 to receive BPD (28-day cycles: belamaf 2.5 mg/kg IV [day 1, cycle 1], 1.9 mg/kg [day 1, cycle 2+] plus pomalidomide 4 mg [days 1‒21, all cycles] and dexamethasone 40 mg [day 1, QW, all cycles]) or PVD (21-day cycles: pomalidomide 4 mg [days 1‒14, all cycles] plus bortezomib 1.3 mg/m² SC [days 1, 4, 8, and 11, cycles 1‒8; days 1 and 8, cycles 9+] and dexamethasone 20 mg [day of and 1 day after bortezomib dose]).

At data cutoff on 29 January 2024, 155 patients received BPD (median LOT, 1) and 147 received PVD (median LOT, 1). Of these, 25 percent and 29 percent had been previously treated with anti-CD38 antibody, respectively. [EHA 2024, abstract LB3440]

Survival benefits

Median PFS was not reached (NR) with BPD (95 percent confidence interval [CI], 20.6‒NR) relative to 12.7 months (95 percent CI, 9.1‒18.5) with PVD (hazard ratio [HR], 0.52, 95 percent CI, 0.37‒0.73; p<0.001) over a median follow-up of 21.78 months. At 12 months, PFS rates were greater with BPD than with PVD (71 percent vs 51 percent).

Objective response rates did not substantially differ between BPD (77 percent, 95 percent CI, 70.0‒83.7) and PVD (72 percent, 95 percent CI, 64.1‒79.2), while the rate of complete response or better was significantly greater with BPD (40 percent, 95 percent CI, 32.2‒48.2) than with PVD (16 percent, 95 percent CI, 10.7‒23.3). In addition, the median duration of response was NR (95 percent CI, 24.9‒NR) with BPD and 17.5 months (95 percent CI, 12.1‒26.4) with PVD.

Follow-up for OS rates among patients with RRMM is still ongoing, but a positive trend was noted in favour of BPD (HR, 0.77, 95 percent CI, 0.53‒1.14).

In terms of safety, adverse events (AEs) occurred both in the BPD (n=150; any grade, >99 percent; grade 3/4, 91 percent) and the PVD arms (n=145; any grade, 96 percent; grade 3/4, 73 percent). About nine in 10 patients (89 percent) treated with BPD experienced ocular AEs (grade 3/4, 43 percent) as opposed to just three in 10 (30 percent) patients who received PVD (grade 3/4, 2 percent).

Serious AEs occurred in 63 percent and 45 percent of patients, respectively, while fatal SAEs arose in 11 percent of patients in both treatment groups. Overall, 15 percent of patients in the BPD arm and 12 percent in the PVD arm stopped treatment due to AEs.

However, “AEs were generally manageable and broadly consistent with the known safety profile of the individual agents,” according to Dimopoulos.

“Use of triplet/quadruplet therapies in the first-line treatment setting for MM raises the need for novel combinations at first relapse, which belamaf combinations may address,” he said.