Belantamab Mafodotin Plus Pomalidomide and Dexamethasone Vs Pomalidomide Plus Bortezomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: A Subset Analysis in Patients Who Have Received 1 Prior Line of Therapy Including Lenalidomide

Background
Use of triplet/quadruplet therapies for 1L multiple myeloma (MM) raises the need for novel combinations at first relapse. In the phase 3 DREAMM-8 (NCT04484623) study, belantamab mafodotin (belamaf) + pomalidomide + dexamethasone (BPd) led to significantly longer progression-free survival (PFS) in the intention-to-treat population than pomalidomide + bortezomib + dexamethasone (PVd) in patients (pts) with relapsed/refractory MM who had received ≥1 prior line of therapy (LOT) including lenalidomide (len). Efficacy of PVd, which was the standard-of-care (SOC) comparator in several trials evaluating BCMA-targeting agents, was similar to previously reported results. Here, we present a post hoc subgroup analysis in 2L pts (at first relapse after 1 prior LOT).

Methods
Pts were randomized 1:1 to BPd (28-day cycles) or PVd (21-day cycles). Response assessments occurred every 4 weeks.

Results
Of the randomized pts, 159 received 1 prior LOT (n=82, BPd; n=77, PVd). All pts were len exposed; 119 (75%) had len-refractory disease (66 [80%] in the BPd arm and 53 [69%] in the PVd arm). Baseline demographic and disease characteristics were generally balanced between arms, except for the presence of extramedullary disease (9 pts in the BPd arm vs 1 in the PVd arm). At data cutoff (Jan 29, 2024), 47 pts (57%) in the BPd arm and 25 (32%) in the PVd arm were still receiving study treatment; 18 pts had died in each arm. Median duration of follow-up was 21.5 mo with BPd and 19.8 mo with PVd.

Among all pts in the 2L (n=159), median PFS (95% CI) was not reached (NR; NR-NR) with BPd and 18.5 mo (12.5 mo-NR) with PVd (HR, 0.50; 95% CI, 0.30-0.85). The 12-mo PFS rate (95% CI) was 78% (67%-86%) with BPd and 64% (51%-74%) with PVd. A complete response or better (CR+) was achieved by 46% (35%-58%) of pts on BPd vs 23% (15%-34%) on PVd; 27/82 (33% [23%-44%]) pts on BPd vs 4/77 (5% [1%-13%]) pts on PVd achieved CR+ and minimal residual disease (MRD) negativity assessed by next-generation sequencing at 10^-5 threshold. Median duration of response (DOR; 95% CI) was NR (NR-NR) with BPd vs 18.0 mo (13.8 mo-NR) with PVd; the 12-mo rate of DOR was 87% (76%-93%) with BPd vs 67% (53%-78%) with PVd.

In pts with len-refractory disease in the 2L, median PFS (95% CI) was NR (21.1 mo-NR) with BPd vs 13.1 mo (9.1-19.8 mo) with PVd (HR, 0.43; 95% CI, 0.25-0.75). The 12-mo PFS rate (95% CI) was 74% (61%-83%) with BPd vs 53% (38%-67%) with PVd. The CR+ and very good partial response or better (VGPR+) rates were higher with BPd (CR+, 44%; VGPR+, 67%) vs PVd (CR+, 21%; VGPR+, 45%); 22/66 (33% [22%-46%]) pts on BPd vs 3/53 (6% [1%-16%]) on PVd achieved CR+ and MRD negativity. The median DOR (95% CI) was NR (NR-NR) with BPd vs 13.8 mo (8.0 mo-NR) with PVd; the 12-mo rate of DOR was 84% (70%-91%) with BPd vs 57% (40%-71%) with PVd.

The safety profile in pts in the 2L was consistent with that in the overall population. Safety analyses included 80 pts on BPd and 77 on PVd. Median (range) overall duration of exposure to any study treatment was 20.5 mo (0.9-34.3 mo) for BPd and 10.8 mo (0.7-35.4 mo) for PVd. Grade 3/4 adverse events (AEs) occurred in 91% of pts on BPd vs 75% on PVd. Fatal serious AEs were reported in 11% of pts on BPd vs 9% on PVd. Thrombocytopenia occurred in 56% of pts (grade ≥3, 38%) on BPd vs 39% (grade ≥3, 25%) on PVd, and neutropenia occurred in 63% of pts (grade ≥3, 54%) on BPd vs 44% on PVd (grade ≥3, 34%).

Grade ≥3 ocular AEs occurred in 36% of pts on BPd vs 3% on PVd. Ocular events in the BPd group were manageable and reversible with dose modifications; they led to treatment discontinuation in 9/80 (11%) pts. A normal best-corrected visual acuity (BCVA) at baseline with postbaseline bilateral worsening of BCVA to 20/50 was reported in 24 pts (30%) treated with BPd. The first event resolved in 22/24 (92%) pts by data cutoff. Of the pts with normal BCVA at baseline (20/25 in ≥1 eye), median (range) time to resolution was 57 days (14-315 days).

Conclusions
In pts in the 2L with prior len exposure, BPd showed robust PFS benefit (HR, 0.50), with deeper and more durable responses than PVd; benefit (HR, 0.43) was maintained in len-refractory disease. The safety profile was consistent with that in the overall population, with manageable AEs. These results support the potential use of BPd as an SOC regimen for len-exposed pts at first relapse, regardless of len refractoriness.

Funding: GSK (Study # 207499)

Drug linker technology licensed from Seagen Inc.; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa.