DREAMM-7 update: Subgroup analyses from a phase 3 trial of belantamab mafodotin (belamaf) + bortezomib and dexamethasone (BVd) vs daratumumab, bortezomib, and dexamethasone (DVd) in relapsed/refractory multiple myeloma (RRMM).
Authors: Maria-Victoria Mateos, Pawel Robak, Marek Hus, Chengcheng Fu, Vera Zherebtsova, Christopher Ward, P. Joy Ho, Ana Carolina de Almeida, Roman Hajek, Kihyun Kim, Meletios Athanasios Dimopoulos, Claudio Cerchione, Nicholas Pirooz, Astrid McKeown, Gbenga Kazeem, Hena Baig, Lydia Eccersley, Sumita Roy-Ghanta, Joanna Opalinska, Vania Hungria
Journal: Journal of Clinical Oncology (2024)

7503 Background: Patients (pts) with RRMM and poor prognostic features, such as high-risk cytogenetics or disease refractory to major drug classes, have an unmet need. In DREAMM-7 (NCT04246047), BVd demonstrated a statistically significant and clinically meaningful progression-free survival (PFS) benefit vs standard-of-care (SOC) DVd in pts with RRMM and ≥1 prior line of treatment (LOT). We present further analyses from DREAMM-7 to better understand efficacy in key subgroups. Methods: Pts with ≥1 prior LOT were randomized (1:1) to BVd, B 2.5 mg/kg IV Q3W + V 1.3 mg/m 2 (D1, 4, 8, 11 of 21-day cycles [C]; up to 8 C) and d 20 mg (D1, 2, 4, 5, 8, 9, 11, 12; up to 8 C), or DVd, D 16 mg/kg (21-day C: C1-3, Q1W; C4-8, Q3W; Q4W from C9 on)—V and d schedules were the same. The primary endpoint was independent review committee–assessed PFS. Secondary endpoints include overall survival (OS), duration of response, and overall response rate (ORR). Pts with high-risk cytogenetics had ≥1 of t(4;14), t(14;16), or del(17p13). Results: The intent to treat (ITT) included 494 pts: BVd, n=243; DVd, n=251. Median PFS (mPFS) in the ITT was 36.6 mo with BVd vs 13.4 mo with DVd (HR, 0.41; 95% CI, 0.31-0.53; P&lt;.00001). ORR in the ITT was 82.7% (95% CI, 77.4%-87.3%) with BVd and 71.3% (65.3%-76.8%) with DVd. BVd had a higher complete response rate vs DVd (34.6% vs 17.1%). At baseline, 79 pts (33%) in the BVd arm and 87 pts (35%) in the DVd arm were refractory to lenalidomide (LEN). In the LEN-refractory subgroup, mPFS favored BVd (25.0 mo; 95% CI, 18.1 mo to NR) vs DVd (8.6 mo; 6.4-13.5 mo) (HR, 0.31; 95% CI, 0.19-0.48). A higher ORR was reported with BVd (84%; 95% CI, 73.5%-90.9%) vs DVd (61%; 49.9%-71.2%) in LEN-refractory pts. In the BVd and DVd arms, 67 (28%) and 69 (27%) pts had ≥1 high-risk cytogenetic abnormality. In the high-risk cytogenetic subgroup, the mPFS was 33.2 mo (95% CI, 20.3 mo to NR) with BVd vs 10.5 mo (7.6-13.4 mo) with DVd (HR, 0.31; 95% CI, 0.18-0.52). ORR favored BVd (85%; 95% CI, 74.3%-92.6%) vs DVd (67%; 54.3%-77.6%) in this subgroup. Additional data including other subgroup analyses will be presented. More deaths occurred with DVd (35%) than BVd (22%) in the ITT; neither arm reached median OS (HR, 0.57; 95% CI, 0.40-0.80; nominal P=.00049). In the ITT, all pts in both arms had ≥1 AE, and 95% (exposure-adjusted rate [exp-adj], 69 per 100 person-years [PY]) of BVd pts and 76% (exp-adj, 62 per 100 PY) of DVd pts reported grade 3/4 AEs. Serious AEs were reported in 50% (exp-adj, 36 per 100 PY) of BVd pts vs 37% DVd (exp-adj, 30 per 100 PY) pts. Ocular AEs were more frequent with BVd vs DVd (79% vs 29%). Conclusions: In DREAMM-7 BVd demonstrated PFS benefit over DVd with an mPFS improvement of 23 mo in pts with RRMM and ≥1 prior LOT. These results, demonstrating efficacy benefit in key subgroups with a high unmet need, support BVd as a potential new SOC in this setting. Clinical trial information: NCT04246047 .