• Two head-to-head phase III trials demonstrated superior efficacy, including overall survival versus a daratumumab-based triplet in DREAMM-7
• Blenrep, a first-in-class anti-BCMA ADC, could transform treatment as early as first relapse where additional effective treatment options are needed

GSK Singapore announced that the Singapore Health Sciences Authority (HSA) has approved Blenrep for the treatment of adults with relapsed or refractory multiple myeloma in combination with bortezomib plus dexamethasone (BVd) in patients who have received at least one prior therapy, and in combination with pomalidomide plus dexamethasone (BPd) in patients who have received at least one prior therapy including lenalidomide.

The approval is based on the favourable benefit risk profile of Blenrep combinations, with efficacy demonstrated in the pivotal DREAMM-7 and DREAMM-8 phase III trials in relapsed or refractory multiple myeloma. These include statistically significant and clinically meaningful progression-free survival (PFS) for Blenrep combinations versus triplet standard of care combinations in both trials and overall survival (OS) versus a daratumumab-based triplet in DREAMM-7.^[2],[3],[4] The safety and tolerability profiles of the Blenrep combinations were broadly consistent with the known profiles of the individual agents.^[2],[3]

Aldo Amador Navarro Rojas, Country Medical Director Singapore, GSK, said: "Today's approval of Blenrep combinations is a redefining moment for patients with relapsed or refractory multiple myeloma in Singapore. While significant progress has been made in the management of multiple myeloma, most patients will eventually experience relapse, highlighting the need for new treatment options that can help extend remission, prolong survival and support quality of life. Backed by the robust results of the DREAMM clinical trial programme, Blenrep offers a differentiated mechanism of action and represents an important addition to the treatment landscape for patients from first relapse onward. "

Approximately 100 to 120 people per year are diagnosed with multiple myeloma in Singapore.^[5] Blenrep is the only anti-BCMA (B-cell maturation antigen) antibody-drug conjugate (ADC) approved in multiple myeloma, providing patients with a differentiated mechanism of action to potentially help slow disease progression and extend survival.^[1] Blenrep combinations provide myeloma patients with additional BCMA-targeting options, which can easily be administered in outpatient settings.

Prof Chng Wee Joo, Senior Consultant, Division of Haematology, Department of Haematology-Oncology, National University Cancer Institute, Singapore, said: "The approval of Blenrep combinations in Singapore adds a new treatment option with a differentiated mechanism of action for patients with relapsed or refractory multiple myeloma. In the DREAMM-7 and DREAMM-8 studies, these regimens demonstrated robust efficacy and can be administered in outpatient settings. These findings suggest the potential to help some patients achieve longer periods of remission while maintaining quality of life and improving outcomes. Importantly, as more patients are living longer with multiple myeloma, preserving quality of life has become an increasingly important treatment goal alongside prolonging survival. This approval expands the available treatment options in the multiple myeloma landscape and provides clinicians with an additional choice for appropriate patients from first relapse onward."

Dr Chandramouli Nagarajan, Senior Consultant, Department of Haematology, Singapore General Hospital, said, "The treatment paradigm of multiple myeloma (MM) is constantly evolving due to new research and identification of newer targets on myeloma cancer cells like B-cell maturation antigen (BCMA) that can be exploited to gain control of the disease. Belantamab mafodotin, in combination with bortezomib or pomalidomide, and dexamethasone, has demonstrated the potential to extend remission and survival effectively through the DREAMM-7 and DREAMM-8 trials. Given the less frequent infusion schedule compared to the current standard of care in relapsed/refractory MM, patients also get to maintain their independence, have time to pursue their meaningful daily activities, and spend valuable time with their loved ones. With the approval of these combinations in Singapore, we have additional options on hand to better support our patients through a fundamentally different approach in the management of relapsed and refractory myeloma patients."

Both DREAMM-7 and DREAMM-8 showed statistically significant and clinically meaningful PFS improvements for the Blenrep combinations compared to standard of care triplet combinations in the second line or later treatment of multiple myeloma.^[2],[3] In DREAMM-7, the Blenrep combination (n=243) nearly tripled median PFS versus the daratumumab-based comparator (n=251) (36.6 months versus 13.4 months, respectively (hazard ratio [HR]: 0.41 [95% confidence interval (CI): 0.31-0.53], p-value<0.00001).^[2] DREAMM-7 also met the key secondary endpoint of OS, showing a statistically significant and clinically meaningful 42% reduction in the risk of death at a median follow-up of 39.4 months favouring the Blenrep combination versus the daratumumab-based comparator (HR: 0.58; 95% CI: 0.43-0.79; p=0.00023). The median OS was not reached in either arm of the study. The three-year OS rate was 74% in the Blenrep combination arm and 60% in the daratumumab combination arm.^[4]

In DREAMM-8, at a median follow-up of 21.8 months, the median PFS was not yet reached (95% CI: 20.6-not yet reached [NR]) with the Blenrep combination compared to 12.7 months in the bortezomib combination (95% CI: 9.1-18.5) at the time of primary analysis.^[3]

Blenrep combinations consistently benefited a broad range of patients, including those with poor prognostic features or outcomes, such as high-risk cytogenetics or those refractory to lenalidomide. Both trials also showed clinically meaningful improvements across all other secondary efficacy endpoints, including deeper and more durable responses versus the respective comparators.^[2],[3]

DREAMM-7 and DREAMM-8 showed that eye-related side effects associated with Blenrep can be managed and reversed with appropriate dose modifications and follow-up. This allowed patients to maintain benefit and resulted in low rates of discontinuation due to eye-related side effects (≤9%) in both trials.^[2],[3] The most commonly reported non-ocular adverse events (>30% of participants) in the Blenrep combination arm were thrombocytopenia (87%) and diarrhoea (32%) in DREAMM-7, and neutropenia (63%), thrombocytopenia (55%) and COVID-19 (37%) in DREAMM-8.^[2],[3]