‘Robust efficacy’ of triplet therapy offers ‘a new standard’ for advanced multiple myeloma
Key takeaways:
- BVd regimen associated with improvement in median duration of response and PFS.
- Deeper responses observed with BVd regimen, including doubling of complete response rate.
A triplet therapy showed significant improvement in PFS compared with the current standard-care regimen among patients with relapsed or refractory multiple myeloma, according to data presented during an ASCO Plenary Series session.
The findings showed that the addition of belantamab mafodotin (Blenrep, GSK) to bortezomib and dexamethasone as second-line therapy resulted in deeper therapeutic responses, more than doubling median duration of response and complete response rates compared with the current standard regimen.
“These results suggest that [belantamab mafodotin plus bortezomib and dexamethasone] can potentially be a new standard of care in second-line or later relapsed or refractory multiple myeloma, owing to the robust efficacy, manageable safety and ease of administration,” Maria-Victoria Mateos, MD, PhD, from Hospital Universitario de Salamanca in Salamanca, Spain, said during a presentation.
Background and methodology
Patients with multiple myeloma can often become refractory to first-line triplet or quadruplet therapy regimens, causing them to relapse and creating a need for effective second-line combinations with new therapy classes, according to Mateos.
Researchers conducted the DREAMM-7 trial to assess the efficacy of the antibody-drug conjugate belantamab mafodotin (Blenrep, GSK) plus bortezomib and dexamethasone (BVd) against the current standard of care of daratumumab (Darzalex, Janssen), bortezomib and dexamethasone (DVd). The analysis included 494 adults with multiple myeloma who received at least one prior line of therapy, no previous treatment with B-cell maturation antigen (BCMA)-targeted therapies, and are not refractory to or intolerant of daratumumab or bortezomib.
Researchers randomly assigned patients in a 1:1 ratio to receive either BVd (n = 243) or DVd (n = 251).
PFS served as the study’s primary endpoint, with OS, duration of response and minimal residual disease as key secondary endpoints.
Results, next steps
At a median follow-up of 28.2 months, researchers reported a significant increase in PFS among patients in the BVd arm, with a median PFS of 36.6 months (95% CI, 28.4 to not reached) among patients in the investigative arm compared with 13.4 months (95% CI, 11.1-17.5) for those in the standard-care arm (HR = 0.41; 95% CI, 0.31-0.53).
Patients in the investigative arm appeared to have longer median duration of response compared with those in the standard-care arm (35.6 months vs. 17.8 months).
Additionally, researchers observed an early trend in OS favoring BVd (HR = 0.57; 95% CI, 0.4-0.8); however, they noted that additional follow-up is ongoing.
Approximately half of patients treated with BVd experienced serious adverse events, according to the data, compared with 37% of patients treated with DVd; meanwhile, ocular effects affected 79% of patients in the BVd cohort and 29% of patients in the DVd group.
The data, according to Mateos, should make BVd the new standard of care for this patient population due to its various measurable improvements.
“A strong and clinically meaningful OS benefit favored the BVd arm vs. the DVd arm,” Mateos said during the presentation. “BVd was associated with deeper responses and led to doubling of [complete response] rates, minimal residual disease negativity rates and median duration of response compared to DVd.”
Perspective
Back to TopDoes DREAMM-7 check all the boxes? It met its primary endpoint of PFS, the OS data looks very favorable, there were no unexpected toxicities and the patient-reported outcomes data are definitely not worse than the comparator arm. Moreover, the regimen can be administered outside the context of large, academic centers with specialized care.
However, the discontinuation rate is a little bit higher than observed with other regimens, and there are questions about sequence of therapy with other BMCA-directed agents, so it would be important as a follow-up to have data on the outcomes of patients who receive subsequent BCMA-directed chimeric antigen receptor T cells or T-cell engagement and treated in the belantamab arm.
The DREAMM-7 trial results are compelling and support the clinical efficacy of belantamab mafodotin for patients with relapsed or refractory multiple myeloma. Although these data come in a crowded field of BMCA-directed therapies, treatment considerations include efficacy, tolerability, as well as access to care. It is important to note that, whereas bispecifics and CAR T cells are required to be done in a setting where cytokine release syndrome can be managed — usually at large academic centers or large practices — belantamab mafodotin can be administered in a community setting.
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Mateos MV, et al. Abstract 439572. Presented at: ASCO Plenary Series, Feb. 7, 2024.
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