According to Suzanne Trudell, MS, MD, PhD, subgroup analyses of outcomes and patient-reported outcomes (PROs) for patients with high-risk characteristics from the Phase 3 DREAMM-7 trial (NCT04246047) and topline findings from the Phase 3 DREAMM-8 trial (NCT04484623), further support the use of berlantamab mafodotin-blmf (Blenrep) in combination with standard of care (SOC) regimens in relapsed/refractory multiple myeloma.1-3
“[DREAMM-7 and DREAMM-8] The two studies were designed in parallel, but when combined, [the data] Berlantamab mafodotin has been shown to work very well when combined with other anti-myeloma drugs,” Trudell said in an interview. On Live®“The safety profile was as expected, [these] “combination”
in 2024 EHA ConferenceResults from the DREAMM-7 trial showed that the combination of berlantamab magofodotin, bortezomib (Velcade), and dexamethasone (BVd) maintained improved progression-free survival (PFS) compared with daratumumab (Darzalex), bortezomib, and dexamethasone (DVd) in both high-risk patients and those resistant to lenalidomide.1 Furthermore, subsequent analysis of PROs from clinical trials showed that overall quality of life (QOL), role functioning, physical functioning, fatigue, and pain were comparable in patients treated with BVd and those treated with DVd.2
moreover, Data from the DREAMM-8 study A trial comparing berlantamab mafodotin plus pomalidomide (Pomalyst) and dexamethasone (BPd) with bortezomib plus pomalidomide and dexamethasone (PVd) has been published. 2024 ASCO Annual MeetingMedian PFS was not reached (NR; 95% CI, 20.6 months to NR) for BPd and 12.7 months (95% CI, 9.1 to 18.5) for PVd (HR, 0.52; 95% CI, 0.37 to 0.73; P Additionally, in difficult-to-treat patient subgroups, including those with high-risk cytogenetic or functional disease, refractory disease after lenalidomide (Revlimid), and prior treatment with anti-CD38 therapy, the BPd regimen reduced the risk of disease progression or death.3
During the interview, Trudell detailed the latest data from the DREAMM-7 and DREAMM-8 studies, discussed the impact these data have on the treatment of patients with relapsed/refractory multiple myeloma, and highlighted the strong efficacy of each treatment regimen.
Trudell is an associate professor at the University of Toronto and a clinical scientist at Canada’s Princess Margaret Cancer Centre.
On LiveWhat previous data reported from DREAMM-7 helped inform the design of DREAMM-8?
efficacy [of adding belantamab mafodotin to standard regimens] It is significant when compared to the control group in both DREAMM-7 and DREAMM-8. [These data] We discuss the robustness of belantamab and mafodotin combination therapy and the early-stage use of these agents.
What is the rationale for considering the addition of berlantamab madodotin to standard Pd in relapsed/refractory multiple myeloma?
The reason is [adding belantamab mafodotin to] The combination of pomalidomide and dexamethasone in DREAMM-8 is based on preclinical studies that have shown synergy with immunomodulatory agents, which are commonly combined with monoclonal antibodies and tend to act synergistically, and this is supported by clinical data with other monoclonal antibodies.
moreover, [the rationale for this research was supported by] of [phase 1/2] ALGONQUIN Research [NCT03715478]This was a pan-Canadian trial looking at the combination of pomalidomide and dexamethasone, and it showed very robust efficacy data and also safety.
What treatments were evaluated in DREAMM-8?
This study was designed to address an unmet need in the current patient population who are progressing after one prior line of therapy, and we knew that this field was evolving and more patients were being treated. [to lenalidomide]and many were resistant to lenalidomide. Based on this need, one of the inclusion criteria was that patients had previous exposure to lenalidomide.
In determining the control group, we wanted to include patients who would also be exposed to anti-CD38, so we chose a non-anti-CD38 control group to allow for enrollment of that patient population, knowing that anti-CD38 agents are moving into the front-line setting.
What efficacy data from the analysis was presented at the 2024 ASCO Annual Meeting?
Results showed that the study met its primary endpoint of PFS, with a clinically meaningful and statistically significant 48% reduction in the risk of death due to progression. All efficacy endpoints favored the combination, including depth and durability of response. There was also a significant trend toward improved OS, with a HR of 0.77. The data demonstrated strong efficacy across all endpoints.
What should I know about the safety profile of BPd?
The safety profile was consistent with the individual drugs in the combination. The most commonly reported adverse events were [AEs] Side effects reported were neutropenia, thrombocytopenia, infections, and ocular toxicity. The ocular toxicities we experienced are consistent with those expected with MMAF-containing antibody-drug conjugates, i.e., belantamab mafodotin. These are commonly reported but were overall reversible in most patients.
What impact do these findings have on clinical practice, and what next steps are planned for this research?
These belantamab and mafodotin combinations represent a new potential standard of care option for patients with early relapse, a patient population that currently represents a clinical gap due to the use of lenalidomide and anti-CD38 in the frontline setting, and as currently available therapies have poor outcomes, this combination offers an option for patients in this setting.
It also provides clinicians with the opportunity to access a commercially available medication and administer it in the community with a very manageable safety profile.
What important data from subgroup analyses of DREAMM-7 were presented at the 2042 EHA meeting?
DREAMM-7, a phase 3 trial comparing berlantamab mafodotin in combination with bortezomib and dexamethasone with DVd, demonstrated a significant improvement in PFS, with an important trend in OS.
At the 2024 EHA meeting, the researchers presented some subgroup analyses, but importantly, they showed data from patients with lenalidomide resistance, which accounted for about one-third of patients in the study. The data showed that the median PFS was [with BVd] 25 months, which is better than the results for lenalidomide-resistant disease with SOC therapy.
They also shared data on high-risk patients, because they’re a particularly difficult patient population to treat, and that data was very interesting because their PFS was consistent with what was seen in the intent-to-treat population, which we haven’t seen in other studies.
Generally, the PFS of high-risk patients always improves, but it usually doesn’t equal the PFS of the intention-to-treat population, and I think that’s an important finding.
What is the importance of learning more about PROs with BVd in this patient population?
Strong Points [are important] “There’s a lot of concern about ocular toxicity and how it affects patients. We know it can affect their ability to drive, read, and watch TV, but overall, I think the quality of life assessments and PROs were stable over the course of treatment. This suggests that BVd doesn’t negatively impact patients’ daily lives.”
References
- Mateos MV, Robak P, Hus M, et al. DREAMM-7 update: subgroup analysis of a phase 3 study comparing berlantamab mafodotin plus bortezomib and dexamethasone with daratumumab, bortezomib, and dexamethasone in relapsed/refractory multiple myeloma. Presented at: 2024 EHA Congress, June 13-16, 2024, Madrid, Spain. Abstract P938.
- Hungria V, Robak P, Hus M, et al. Patient-reported outcomes from DREAMM-7, a randomized phase 3 study comparing belantamab mafodotin, bortezomib + dexamethasone (dex) with daratumumab, bortezomib + dex in relapsed/refractory multiple myeloma. Presented at: 2024 EHA Congress, June 13-16, 2024, Madrid, Spain. Abstract P945.
- Trudel S, Beksac M, Pour L, et al. Results of the randomized phase 3 DREAMM-8 trial comparing berlantamab mafodotin plus pomalidomide and dexamethasone (BPd) with pomalidomide plus bortezomib and dexamethasone (PVd) in relapsed/refractory multiple myeloma (RRMM). J Clinical Oncol..2024;(Suppl 17):LBA105.
