Patients with Relapsed/Refractory multiple myeloma who achieved sustained minimal residual disease negativity in the dreamm-7 trial

Abstract Introduction: In the phase 3 DREAMM-7 trial (NCT04246047), belantamab mafodotin (belamaf) plus bortezomib and dexamethasone (BVd) demonstrated significant progression-free survival (PFS) and overall survival (OS) benefits vs daratumumab plus bortezomib and dexamethasone (DVd) in patients with relapsed/refractory multiple myeloma (RRMM) who had received ≥1 prior line of therapy (LOT). Minimal residual disease (MRD) negativity has been shown to be a predictor of PFS and OS in multiple myeloma. The first interim analysis of the DREAMM-7 trial (data cutoff: October 2, 2023) showed that patients in the BVd arm had a significantly higher rate of complete response (CR)–based MRD negativity vs those in the DVd arm. MRD was declared statistically significant at the second interim analysis (data cutoff: October 7, 2024) due to the prespecified testing hierarchy. The purpose of the current analysis was to evaluate the number of patients who achieved sustained MRD negativity for ≥12 months in the DREAMM-7 trial and to describe their demographics and baseline disease characteristics. Methods: As previously reported, patients treated with ≥1 prior LOT were randomized (1:1) to BVd or DVd in DREAMM-7. The primary endpoint was independent review committee–assessed PFS. OS and MRD negativity at achievement of ≥ CR were key secondary endpoints. Patients achieving ≥ CR were tested for MRD negativity by next-generation sequencing with 10−5 sensitivity and 10−6 sensitivity (exploratory analysis). Results: At data cutoff (October 7, 2024), CR–based MRD negativity rates in pts with ≥ CR were 70% (61/87) vs 59% (26/44) in the BVd vs DVd arms, respectively, at the 10−5 sensitivity threshold; rates in the intention-to-treat (ITT) population were 25% (95% CI, 19.8%-31.0%) vs 10% (95% CI, 6.9%-14.8%). At the 10−6 sensitivity threshold, rates in patients with ≥ CR were 45% (39/87) vs 23% (10/44) in the BVd vs DVd arms, respectively; rates in the ITT population were 16% (95% CI, 11.7%-21.3%) vs 4% (95% CI, 1.9%-7.2%). Median time to first CR–based MRD negativity was 11.14 months in the BVd arm vs 17.02 months in the DVd arm. Sustained ≥ CR MRD negativity was observed for ≥12 months in 57% (35/61) of patients who reached MRD negative status in the BVd arm vs 42% (11/26) of patients in the DVd arm. In patients who had sustained MRD negativity for ≥12 months, age was balanced between treatment arms. All patients had Revised International Staging System stages of I or II at screening. The DVd arm had a greater proportion of patients with 1 prior LOT (91%) vs the BVd arm (63%); the remaining patients in both arms received ≥2 prior LOTs. The proportion of patients with high-risk cytogenetics was greater in the BVd arm (40%) vs the DVd arm (27%). Conclusions: BVd demonstrated greater overall MRD negativity rates at 10−5 and 10−6 thresholds compared with DVd. In addition, for those patients achieving MRD negativity, more patients had sustained MRD-negative status for ≥12 months in BVd arm compared with DVd arm, further demonstrating the link between achieving deep and durable treatment responses. Funding: GSK (study ID, 207503). Drug-linker technology licensed from Seagen Inc; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa.