DREAMM-7: exploratory patient-reported outcomes in relapsed or refractory multiple myeloma

Evidence before this study

Therapies targeting BCMA represent a novel therapeutic approach for relapsed or refractory multiple myeloma. Belantamab mafodotin is a first-in-class antibody-drug conjugate comprising a humanised, afucosylated BCMA monoclonal antibody conjugated to the microtubule inhibitor, monomethyl auristatin F, which has demonstrated robust single-agent anti-myeloma activity in relapsed or refractory multiple myeloma. We searched PubMed for medical literature published between Jan 1, 2000, and Nov 15, 2024, using the search terms “relapsed or refractory” AND “multiple myeloma” AND “BCMA” AND “clinical trial”. We identified several anti-BCMA agents—including chimeric antigen receptor T-cell therapies and bispecific antibodies—that are in clinical development for the treatment of multiple myeloma. However, no publications evaluating BCMA antibody-drug conjugates other than belantamab mafodotin were identified.

Belantamab mafodotin with bortezomib and dexamethasone was evaluated in DREAMM-7, an ongoing phase 3, randomised study comparing belantamab mafodotin, bortezomib, and dexamethasone with daratumumab, bortezomib, and dexamethasone, a standard of care for patients with relapsed or refractory multiple myeloma who have received at least one previous line of therapy. Belantamab mafodotin demonstrated a significant progression-free survival benefit compared with daratumumab (HR 0·41, 95% CI 0·31–0·53; p<0·001), as well as a significant and clinically meaningful improvement in overall survival (HR 0·58, 95% CI 0·43–0·79; p=0·00023). The safety profile of belantamab mafodotin, bortezomib, and dexamethasone was consistent with previous findings. Ocular events, a known risk with belantamab mafodotin, were manageable with dose delays and reductions; overall health-related quality of life did not differ substantially between belantamab mafodotin and daratumumab.

To gain a full understanding of the benefits of belantamab mafodotin treatment and the effect on symptoms, tolerability, and functioning, DREAMM-7 assessed patient-reported outcomes as secondary and exploratory objectives.

Added value of this study

Health-related quality of life was generally maintained or improved over time with both belantamab mafodotin and daratumumab, with symptomatic adverse events being of minimal severity. Based on post-hoc analyses, ocular side-effects appeared to have a minor effect on health-related quality of life. Of the symptomatic adverse events assessed in these analyses, fatigue and decreased appetite had the greatest negative effect on quality of life.

Implications of all the available evidence

The significant benefit in progression-free survival, the minimal impact on health-related quality of life, and a manageable safety profile support the use of belantamab mafodotin with bortezomib and dexamethasone as a potential new standard of care in patients with relapsed or refractory multiple myeloma who have received at least one previous line of therapy.

Source: The Lancet Haematology