Positive results were reported for belantamab mafodotin-blmf plus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma, according to data from the phase III DREAMM-7 study presented at the ASCO Plenary Series: February 2024 Session (Abstract 439572). DREAMM-7 evaluated the triplet therapy of belantamab mafodotin, bortezomib, and dexamethasone (BVd) vs daratumumab, bortezomib, dexamethasone (DVd), finding a significant improvement in progression-free survival, a doubling in depth of response, and a strong trend toward better overall survival with BVd in patients with relapsed or refractory multiple myeloma.
“BVd demonstrated a statistically significant and clinically meaningful progression-free survival benefit, with a median progression-free survival that was 23 months longer than with DVd,” said Maria-Victoria Mateos Manteca, MD, PhD, of the Hospital Universitario de Salamanca in Salamanca, Spain.
Maria-Victoria Mateos Manteca, MD, PhD
Belantamab mafodotin is an antibody-drug conjugate targeting B-cell maturation antigen (BCMA). Prior disappointing findings from the phase III confirmatory DREAMM-3 trial led to the voluntary withdrawal of belantamab mafodotin in November 2022. That study compared single-agent belantamab mafodotin to pomalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma and failed to show a significant improvement in progression-free survival.
About DREAMM-7
DREAMM-7 enrolled 494 patients with multiple myeloma previously treated with at least one prior line of therapy. Patients were randomly assigned to receive BVd or DVd. Belantamab mafodotin was given at 2.5 mg/kg every 3 weeks, and daratumumab was dosed according to standard protocol. For cycle 9 and onward, both belantamab mafodotin and daratumumab were given as single agents every 3 weeks and 4 weeks, respectively. The primary endpoint was progression-free survival.
Baseline characteristics were similar between the treatments arms. About half the patients in each arm had stage II disease, and half had received one prior regimen. Approximately 27% of patients in each arm had high-risk cytogenetics; 5% of those in the BVd arm and 10% of those in the DVd arm had extramedullary disease. One-third were refractory to lenalidomide and more than two-thirds had undergone a stem cell transplant.
Robust Benefit Seen With BVd
After a median follow-up period of 28.2 months, the median progression-free survival was 36.6 months in the BVd arm and 13.4 months in the DVd arm (hazard ratio [HR] = 0.41, P < .0001). The progression-free survival benefit consistently favored BVd vs DVd across prespecified subgroups, including patients with lenalidomide-refractory (HR = 0.37) or high-risk cytogenetic (HR = 0.36) myeloma, Dr. Mateos reported.
“Overall survival showed an early, strong, and clinically meaningful trend favoring the BVd arm as well,” she reported. Median overall survival was not reached in either arm, with events recorded for 22% of those in the BVd arm and 35% of those in the DVd arm (HR = 0.57, P = .00049). The threshold for overall survival statistical significance in the trial was P ≤ .00037. Follow-up for overall survival is ongoing.
BVd was also associated with a greater depth of response and high rates of undetectable measurable residual disease (MRD); rates for both outcomes were doubled with BVd over DVd, she noted. A complete response or stringent complete response was achieved by 34.6% of patients receiving BVd vs 17.1% receiving DVd, and undetectable MRD was observed in 38.7% vs 17.1%, respectively (P < .00001). Median duration of response was 35.6 months vs 17.8 months, with 76% and 49% of patients, respectively, maintaining responses at 18 months, she reported.
Manageable Safety Profile
Half of the patients treated with BVd experienced serious adverse effects compared to 37% of those treated with DVd; drug exposure was higher in the BVd arm, she noted. Commenting on nonocular toxicities, Dr. Mateos said the safety and tolerability of the BVd regimen was consistent with the known safety profile of the individual agents.
Ocular adverse effects, which have been of concern with belantamab mafodotin, were experienced by 79% of patients in the BVd arm and 29% in the DVd arm, with grade ≥ 3 toxicities observed in 34% and 3%, respectively. Patients primarily reported blurred vision (66% overall, grade ≥ 3 in 22%), followed by dry eyes, eye irritation, and visual impairment, which was grade ≥ 3 for each toxicity in 7% or fewer patients. Ocular adverse events led to dose reductions in 44%, dose interruptions in 78%, and treatment discontinuation in 9% of BVd-treated patients, but were reversible in almost all. No differences were seen in global quality of life over time between the arms, Dr. Mateos said.
“These results suggest that BVd can potentially be a new standard of care in second-line [treatment] or later [of] relapsed and refractory multiple myeloma, owing to the robust efficacy, manageable safety, and ease of administration,” Dr. Mateos said. She added that this recommendation applies irrespective of prior exposure to immunomodulatory drugs or protein inhibitors.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
