In R/R Myeloma, Belantamab Mafodotin/BorDex Outperforms Standard Treatment

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According to an interim analysis of the DREAMM-7 trial, belantamab mafodotin, bortezomib, and dexamethasone achieved a statistically significant and clinically meaningful improvement in progression-free survival among patients with multiple myeloma.

Maria-Victoria Mateos, MD, PhD

Maria-Victoria Mateos, MD, PhD

In a head-to-head comparison, the combination of belantamab mafodotin (Blenrep) with bortezomib (Velcade) and dexamethasone (BorDex) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) vs daratumumab (Darzalex) plus BorDex in the second line and later treatment of patients with relapsed or refractory multiple myeloma, meeting the primary end point of the phase 3 DREAMM-7 trial (NCT04246047).1

Findings come from an interim analysis of the phase 3 DREAMM-7 trial which were presented at the American Society of Clinical Oncology (ASCO) Plenary Series: February Session. At a median follow-up of 28.2 months (range, 0.10-40 months), the combination of belantamab mafodotin and BorDex (n = 243) produced a median PFS of 36.6 months (95% CI, 28.4-not reached [NR]) and led to a 59% reduction in risk of disease progression or death (HR, 0.41; 95% CI, 0.31-0.53; P <.00001) vs 13.4 months (95% CI, 11.1-17.5) with the standard-of-care daratumumab combination (n = 251). The treatment improved PFS across all prespecified subgroups, including those resistant to lenalidomide (Revlimid) and those with high-risk cytogenetic features.

Further, there was a clinically meaningful trend in overall survival (OS) which favored the belantamab mafodotin and BorDex combination with a 43% reduction in risk of death (HR, 0.57; 95% CI, 0.40-0.80; P =.00049), which has not yet reached the interim criteria for statistical significance of OS.

“These results support the belantamab mafodotin combination as a potential new standard-of-care option for these patients with the magnitude of benefit seen in progression-free survival, showing a 59% reduction in the risk of disease progression or death and strong trend in overall survival,” Maria-Victoria Mateos, MD, PhD, head of myeloma and clinical trials unit, hematology department and professor of medicine at the University of Salamanca, Spain, and DREAMM-7 principal investigator, told Targeted OncologyTM.

Multiple Myeloma: © David A Litman - stock.adobe.com

Multiple Myeloma: © David A Litman - stock.adobe.com

DREAMM-7 is a multicenter, open-label, randomized, phase 3 trial assessing belantamab mafodotin in combination with BorDex vs daratumumab and BorDex in patients with relapsed/refractory multiple myeloma who previously were treated with at least 1 prior line of multiple myeloma therapy.2

Patients were required to have documented disease progression during or after their most recent therapy. Investigators aimed to evaluate the safety and efficacy of the combination. Enrollment was also open to patients with adequate organ function and an ECOG performance status of 0 to 2. All prior treatment-related adverse events (AEs) must have resolved to grade 1 or lower with the exception of alopecia.3

The study randomized 494 patients in a 1:1 ratio to receive either the belantamab mafodotin 2.5mg/kg given intravenously every 3 weeks with BorDex or daratumumab plus BorDex. Patients received treatment until the end of the study, withdrawal of consent, progressive disease, death, or unacceptable toxicity.

In addition to the primary end point of PFS, secondary end points explored in the trial were OS, duration of response (DOR), and minimal residual disease (MRD) negativity rate as assessed by next-generation sequencing. Regarding the secondary end points, findings were clinically meaningful with the belantamab mafodotin combination, including a doubling of complete response (CR) rate, MRD negativity rate, and median DOR.1

In the experimental vs control arms, the median age of patients was 65.0 years (range, 34-86) vs 64.0 (range, 32-89), 128 (85%) vs 144 (57%) were male, 206 (85%) vs 203 (81%) were White/Black or African American, and 96% of patients in both arms had an ECOG performance status greater than or equal to 1.

“Baseline characteristics of the patients were well balanced. Of note, 28% and 27% in the belantamab and daratumumab arms had a high risk of cytogenetic abnormalities, respectively, and 5% in the belantamab arm and 10% in the daratumumab arm had extramedullary disease. Prior treatments were also balanced between items,” explained Mateos in the presentation.

With the belantamab combination vs daratumumab combination, approximately half of the patients (51% and 50%) had and 1 private prior of therapy with most patients having been previously treated with a proteasome inhibitor, typically bortezomib (86% vs 84%). Eighty-one percent and 86% of patients were treated with a prior immunomodulatory agent.

In the belantamab combination arm vs daratumumab and BorDex arm, the overall response rates were 82.7% (95% CI, 77.4%-87.3%) vs 71.3% (range, 65.3%-76.8%). Stringent CR rates were 14% vs 5.2%, CR rates were 20.6% vs 12%, very good partial response (PR) rates were 31.3% vs 29.1%, and PRs were 16.9% vs 25.1%. The MRD negativity rate was 24.7 (95% CI, 19.4-30.6; P <.00001) with the belantamab mafodotin plus BorDex combination vs 9.6 (95% CI, 6.2-13.9; P <.00001) daratumumab plus BorDex combination, and the median DORs were 35.6 months (95% CI, 30.5-NR) vs 17.8 months (95% CI, 13.8-23.6). Responses are ongoing for over half of patients in the belantamab/BorDex arm.

“These results from DREAMM-7 show how belantamab mafodotin in combination with bortezomib and dexamethasone represents a significant improvement over the daratumumab-based regimen, a current standard-of-care, in a second-line or later multiple myeloma treatment setting,” Mateos told Targeted Oncology.

For safety, the belantamab mafodotin combination had a safety and tolerability profile that was consistent with the known profile of each individual agent. In the belantamab mafodotin combination and daratumumab combination arms, non-ocular AEs of clinical interest which were grade 3 or higher included thrombocytopenia (55% and 35%), neutropenia (12% and 6%), pneumonia (12% and 4%), and anemia (8% and 10%), respectively.

AEs related to the eye were generally reversible and manageable with dose modification.

Grade 3 or higher ocular AEs were seen in 34% of patients treated with the belantamab mafodotin combination. These were primarily blurred vision (22%), dry eye (7%), eye irritation (5%), and visual impairment (5%). A total of 82 patients (34%) with a best corrected visual acuity score of 20/25 or better in at least 1 eye at baseline had a worsening in both eyes to 20/50 or worse, and 98% of these patients AEs had resolved at the time of the analysis with a median time to resolution of 22 days.

A total of 44% of patients had dose reductions, 78% of patients had dose delays or interruptions, and 9% of patients discontinued due to any ocular event. Additionally, there was no difference observed between arms over time in regard to global quality-of-life, as measured by EORTC QLQ-C30 scale.

The follow-up for OS continues and further analyses are planned.

“Anti-BCMA therapies are helping to improve outcomes for patients with multiple myeloma, but they are currently used in later lines of treatment, and most are administered in a hospital setting in multiple myeloma centers of excellence,” Mateos told Targeted Oncology. “Belantamab mafodotin in combination with BorDex could offer the potential for a BCMA-targeted treatment option with wide patient eligibility and an in-office infusion process in a community oncology treatment center, potentially improving the patient experience.”

REFERENCES:
  1. Mateos MV, Robak P, Hus M, et al. Results from the randomized phase III DREAMM-7 study of belantamab mafodotin (belamaf) + bortezomib, and dexamethasone (BVd) vs daratumumab, bortezomib, and dexamethasone (DVd) in relapsed/refractory multiple myeloma (RRMM). Presented at: 2024 February ASCO Plenary Series. Abstract 439572.
  2. DREAMM-7 phase III trial shows Blenrep combination nearly tripled median progression-free survival versus standard of care combination in patients with relapsed/refractory multiple myeloma. News release. GSK plc. February 5, 2024. Accessed February 6, 2024. http://tinyurl.com/2t4rsme7
  3. Evaluation of efficacy and safety of belantamab mafodotin, bortezomib and dexamethasone versus daratumumab, bortezomib and dexamethasone in participants with relapsed/refractory multiple myeloma (DREAMM 7). ClinicalTrials.gov. Updated December 13, 2023. Accessed February 6, 2024. https://clinicaltrials.gov/study/NCT04246047

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