Dr Dimopoulos on Efficacy Findings From the DREAMM-8 Trial in Multiple Myeloma

Meletios (Thanos) Dimopoulos, MD, professor, therapeutics, Hematology Oncology, National and Kapodistrian University of Athens School of Medicine, discusses the design of and findings from the phase 3 DREAMM-8 trial (NCT04484623) investigating belantamab mafodotin-blmf (Blenrep), pomalidomide (Pomalyst), and dexamethasone (BPd) in patients with multiple myeloma.

The prospective DREAMM-8 trial randomly assigned patients to receive BPd or pomalidomide, bortezomib (Velcade), and dexamethasone (PVd). Patients were eligible for enrollment if they had received 1 to 3 prior lines of therapy. All patients were required to have received prior treatment with lenalidomide (Revlimid), which Dimopoulos notes is relevant to current clinical practice in this disease, as most patients in this population currently receive lenalidomide maintenance therapy. In DREAMM-8, 23% and 27% of patients in the BPd and PVd arms, respectively, had also received prior treatment with the anti-CD38 monoclonal antibody daratumumab (Darzalex).

Progression-free survival (PFS) served as the primary end point of the trial; this end point was met, with patients in the BPd arm achieving a median PFS that was not reached vs 12.7 months (95% CI, 9.1-18.5) among those in the PVd arm (HR, 0.52; 95% CI, 0.37-0.73; 2-sided 

 < .001). This PFS improvement with BPd was both statistically significant and clinically meaningful, Dimopoulos highlights. Additionally, responses were deeper in the BPd arm; the overall response rate was 77% (95% CI, 70%-84%) in this arm vs 72% (95% CI, 64%-79%) in the control arm. The respective complete response (CR) or better rates were 40% (95% CI, 32%-48%) and 16% (95% CI, 11%-23%). Moreover, 24% (95% CI, 17%-31%) of patients in the BPd arm achieved a CR or better plus minimal residual disease negativity vs 5% (95% CI, 2%-10%) of those in the PVd arm. The estimated percentages of patients with a duration of response of 12 months were 79% (95% CI, 71%-86%) in the BPd arm vs 61% (95% CI, 50%-70%) in the PVd arm.

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Meletios Dimopoulos, MD, discusses the design of and findings from the DREAMM-8 trial investigating BPd in patients with multiple myeloma.

Meletios A. Dimopoulos, MD, discusses patient-reported outcomes with BPd in pretreated patients with relapsed/refractory multiple myeloma.

Dr Dimopoulos on Patient Reported Outcomes With BPd in Pretreated R/R Multiple Myeloma

Meletios A. Dimopoulos, MD, professor and chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine, Greece, discusses patient-reported outcomes (PROs) with belantamab mafodotin-blmf (Blenrep) plus pomalidomide (Pomalyst) and dexamethasone (BPd) vs bortezomib (Velcade) plus pomalidomide and dexamethasone (VPd) in pretreated patients with relapsed/refractory multiple myeloma.

(NCT04484623) were presented during the 

2024 International Myeloma Society Annual Meeting

. From week 5 to 137, no significant differences in global health status or quality of life (QOL) scores were observed between the BPd (n = 133) and VPd (n = 124) arms, as measured by the EORTC QLQ-C30, Dimopoulos begins. Scores for role functioning, physical functioning, fatigue, and disease symptoms/pain were also comparable across both treatment arms. Measurable improvements in pain and the functional ability were evident, he notes.

However, a higher proportion of patients in the BPd arm achieved meaningful improvements (≥10 points) in EORTC scores compared with the VPd arm, especially in physical functioning (53.6% vs 31.3%) and fatigue (65.2% vs 46.3%), were particularly evident in of the states. Other notable improvements were seen in GHS/QOL (49.0% vs 39.5%), role functioning (51.6% vs 39.5%), and disease symptoms (56.8% vs 43.5%).

Regarding ocular toxicity, belantamab mafodotin is known to cause microcystic keratitis, leading to blurred vision, Dimopoulos continues . At the start of the trial, more patients in the BPd arm (73%) reported worsening vision-related function compared with the VPd arm (51%), based on OSDI scores. However, 92% of BPd-treated patients (n = 110) later reported improvements in vision after a median of 57 days, he reports. This improvement is likely due to dose adjustments and the use of extended treatment intervals, which help mitigate the ocular toxicity of belantamab mafodotin, Dimopoulos explains.

These QOL benefits, combined with the significant progression-free survival advantage seen with BPd over VPd in DREAMM-8, suggest that BPd could become a new standard of care for relapsed/refractory multiple myeloma, he concludes.

Meletios A. Dimopoulos, MD, discusses patient-reported outcomes with BPd in pretreated patients with relapsed/refractory multiple myeloma.
 

Results from the randomized phase 3 DREAMM-8 study

Results from the randomized phase 3 DREAMM-8 study of belantamab mafodotin plus pomalidomide and dexamethasone (BPd) vs pomalidomide plus bortezomib and dexamethasone (PVd) in relapsed/refractory multiple myeloma (RRMM)

DREAMM-8 (NCT04484623) is an ongoing, randomized, open-label, phase 3 study evaluating BPd vs PVd in patients with RRMM previously treated with ≥1 line of therapy including lenalidomide.

Results From the Randomized Phase 3 DREAMM-8 Study of Belantamab Mafodotin Plus Pomalidomide and Dexamethasone (BPd) vs Pomalidomide Plus Bortezomib and Dexamethasone (PVd) in Relapsed/Refractory Multiple Myeloma (RRMM)

Meletios A. Dimopoulos, MD, professor and chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University Athens School of Medicine, discusses the goal of the phase 3 ASPEN trial in Waldenström macroglobulinemia.

In an effort to demonstrate that a novel BTK inhibitor may be more advantageous than ibrutinib (Imbruvica), investigators designed the randomized ASPEN study, says Dimopoulos. 

Waldenström macroglobulinemia is a rare disease. As such, few prospective, randomized trials have been performed within the space to date, explains Dimopoulos. The primary end point of the ASPEN trial was to see whether the administration of zanubrutinib (Brukinsa) could result in a superior complete response rate and very good partial response rates compared with ibrutinib. 

Furthermore, patients were evaluated for an 

 mutation, which is known to present in the majority of patients with Waldenström macroglobulinemia,; those with the 

 mutation were eligible for inclusion in the study, concludes Dimopoulos.

Meletios A. Dimopoulos, MD, discusses the goal of the phase 3 ASPEN trial in Waldenström macroglobulinemia.

Dr. Dimopoulos on the Goal of the ASPEN Trial in Waldenström Macroglobulinemia

Meletios A. Dimopoulos, MD, professor and chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University Athens School of Medicine, in Athens, Greece, discusses the utility of zanubrutinib (Brukinsa) in Waldenström macroglobulinemia.

In August 2018, the combination of ibrutinib (Imbruvica) and rituximab (Rituxan) became the first regimen to receive regulatory approval for the treatment of patients with Waldenström macroglobulinemia, says Dimopoulos.

Zanubrutinib is a next-generation BTK inhibitor that could maximize BTK occupancy and minimize off-target inhibition that is associated with earlier generation BTK inhibitors, explains Dimopoulos.

Additionally, zanubrutinib appears to have favorable drug-drug interaction properties, which could aid in the administration of this agent, concludes Dimopoulos.

Meletios A. Dimopoulos, MD, discusses the utility of zanubrutinib (Brukinsa) in Waldenström macroglobulinemia.



Dr. Dimopoulos on the Utility of Zanubrutinib in Waldenström Macroglobulinemia

Meletios A. Dimopoulos, MD, professor and chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University Athens School of Medicine, in Athens, Greece, discusses safety results from the randomized phase 3 ASPEN trial of zanubrutinib (Brukinsa) in patients with Waldenström macroglobulinemia presented at the 2020 

In the trial, investigators discovered an advantage with the investigational, next-generation BTK inhibitor zanubrutinib compared with ibrutinib (Imbruvica) in terms of adverse events that resulted in death, discontinuation of treatment and dose reductions, says Dimopoulos. Additionally, zanubrutinib showed lower rates of atrial fibrillation, contusion, diarrhea, hypertension, muscle spasms, pneumonia, and bleeding Dimopoulos adds.

Zanubrutinib demonstrated clinically meaningful advantages in terms of safety and tolerability, Dimopoulos concludes.

Meletios A. Dimopoulos, MD, discusses safety results from the randomized phase 3 ASPEN trial of zanubrutinib (Brukinsa) in patients with Waldenström macroglobulinemia.

Dr. Dimopoulos on the Safety of Zanubrutinib in Waldenström Macroglobulinemia

Meletios A. Dimopoulos, MD, professor and chairman of the Department of Clinical Therapeutics at the University Athens School of Medicine, Athens, Greece, discusses the evolution of selinexor in multiple myeloma.

Selinexor is an oral, selective inhibitor of nuclear export that blocks exportin 1, that leads to the nuclear accumulation and reactivation of tumor suppressor proteins. The drug had shown activity when used in combination with low-dose dexamethasone in the phase 2 STORM trial. In July 2019, the FDA granted an accelerated approval to selinexor for use in combination with dexamethasone for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 4 prior therapies and whose disease is refractory to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and a CD38-targeted monoclonal antibody.

The next logical step was to evaluate the drug in combination with other active agents in earlier lines of therapy, says Dimopoulos. To that end, the phase 3 BOSTON trial was launched and patients who had received between 1 and 3 prior lines of therapy were randomized to receive the combination of selinexor plus bortezomib (Velcade) and dexamethasone or bortezomib and dexamethasone alone. The results of the trial were presented during the 

Meletios A. Dimopoulos, MD, discusses the evolution of selinexor in multiple myeloma.

Meletios A. Dimopoulos, MD

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