The ‘Trojan horse’ drug offers Australians renewed hope and improved quality of life.
The first antibody-drug conjugate for multiple myeloma has been registered in Australia for use in combination with standard therapies for relapsed or refractory disease.
The therapy has been described as a “Trojan horse” for its ability to target myeloma cells and deliver cytotoxic therapy from within, and represents the first drug of its kind approved for multiple myeloma in the country.
Belantamab mafodotin (Blenrep, GSK) has been approved in Australia for adults with multiple myeloma whose disease has relapsed or become refractory to initial therapy, offering clinicians a novel treatment option as part of a triple combination.
The antibody-drug conjugate (ACD) combines a monoclonal antibody targeting B-cell maturation antigen (BCMA) on myeloma cells with an anti-cancer agent.
Once attached to malignant plasma cells, it delivers the cytotoxic payload directly inside the cells, while also aiding the immune system in recognising and clearing cancer cells.
The approval follows extensive international and Australian clinical trials, including pivotal Phase 3 studies conducted at 22 sites nationwide.
Despite therapeutic advances over the past decade, multiple myeloma remains largely incurable, and most patients will eventually relapse or develop resistance to standard treatments.
Professor Hang Quach, Director of Clinical Haematology and Haematology Research at St Vincent’s Hospital, said initial regimens typically involved three or more agents, but follow-up treatment options become increasingly limited.
She told Oncology Republic there was a significant unmet need for innovative therapies with different mechanisms of action to improve long term outcomes and quality of life for myeloma patients.
“Despite advances, we know most patients with multiple myeloma will relapse,” she said.
“Each relapse becomes harder to treat, and so for the more than 2000 Australians diagnosed each year with myeloma and many, many more living with disease right now, having any effective options at the time of relapse is absolutely critical.
“Belantamab mafodotin represents a new generation of targeted therapy called antibody drug conjugates – so think of it like a Trojan horse or target bomb for cancer cells.
“This drug is built to recognise and bind to a marker that is specifically present on myeloma cells called BCMA, and upon binding to the myeloma cells, it delivers a tiny amount of very powerful cancer killing drug straight into the myeloma cell.”
Rather than “blasting the whole body like traditional chemotherapy, which we do for cancer up until now”, this therapy focuses the chemotherapy only where it’s needed.
“This is very novel and it’s a very exciting drug,” she told OR.
The registration of therapy was based on data from the open-label, randomised DREAMM-7 study which compared Belantamab mafodotin in combination with bortezomib and dexamethasone (BVd) to daratumumab in combination with bortezomib and dexamethasone (DVd) in patients with relapsed or refractory multiple myeloma, and the DREAMM-8 study, which compared Blenrep in combination with pomalidomide and dexamethasone (BPd) to pomalidomide, bortezomib and dexamethasone (PVd).
In DREAMM-7, BVd demonstrated almost triple the median progression-free survival (PFS) vs DVd, with 36.6 months compared to 13.4 months, which was the primary endpoint of the study (HR= 0.41; 95% CI: 0.31, 0.53; p<0.001).
At a median follow-up of 39.4 months, treatment with BVd also demonstrated statistically significant overall survival (OS) benefit compared to DVd indicating a 42% reduction in risk of death (HR 0 58;9 % C I :0. 43-0 79, p=0.0002). The predicted median OS , based on post-hoc analysis was 84 months in patients treated with BVd compared to 51 months in patients treated with DVd.
In DREAMM-8, patients treated with BPd had a statistically significant improvement in PFS in the overall population comparted with PVd. PFS was maintained in all prespecified subgroups. This included patients with high-risk cytogenetics [HR 0.57 (95% CI 0.34, 0.95), the median PFS was 17.6 months for BPd and 9.1 months for PVd.
In those refractory to lenalidomide [HR 0.45 (95% CI 0.31, 0.65), the median PFS was 24 months for BPd and 9.2 months for PVd, and in patients refractory to anti-CD38 agents [HR 0.65 (95% CI 0.36. 1.18), median PFS was 11.5 months for BPd and 6.4 months for PVd.
Professor Quach said the next important step was the consideration of the drug for PBS listing. The therapy is currently not funded on the Pharmaceutical Benefits Scheme, with reimbursement currently under consideration by the Pharmaceutical Benefits Advisory Committee.
“If successful then this drug will be accessible to all Australians who need it,” she said.
“And I think for patients and families, this approval offers something very real, and that’s hope. The drug offers better remission, better quality of life, and even after relapse, we still have an effective tool to fight this disease, and that’s something to hope for. And I think this is very meaningful for the myeloma community in Australia.”
Belantamab mafodotin can be used in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy, or with pomalidomide and dexamethasone in those previously treated with lenalidomide.
It is administered as a 30-minute outpatient infusion, allowing treatment without hospitalisation. Common side effects include fever, fatigue, gastrointestinal symptoms, and blood count abnormalities, while ocular toxicity is a notable risk that requires pre-dose and periodic eye examinations.
Dose adjustments may be necessary if vision changes occur, and clinicians are advised to report adverse events to the Therapeutic Goods Administration for ongoing safety monitoring.
Professor Quach said it was important to note that the eye-related side effects were “virtually all reversible”.
“This is probably one of the most well-tolerated drugs that I’ve used in multiple myeloma, that is convenient and the ocular or the eye associated adverse events are reversible and very manageable if the doctor is very used to the drug,” she said.
Mark Henderson, CEO of Myeloma Australia, highlighted the growing need for new therapies as more than 2600 Australians are diagnosed with multiple myeloma each year and fewer than 60% survived five years post-diagnosis.
“Blenrep provides a new choice for patients at a critical point in their treatment journey,” he said.
Professor Quach said she had high hopes that drugs like Belantamab mafodotin would change the long-term prognosis for many myeloma patients.
“In Australia, the median or the average lifespan of people living with myeloma in Australia is quoted about maybe five to seven years based on our registry data,” she told OR.
“But in reality, I think if we bring these types of drugs forward and offer it to people who need it, I dare say that a proportion of people, if not many people, will probably reach their natural lifespan in the years to come.”
Andrew Thomas, vice-president and general manager at GSK Australia said the company had been focused on exploring novel therapies to improve outcomes for a group of patients for whom there were “limited treatment options”.
“That is why we have been focussed on exploring how novel combination therapies with differentiated mechanisms of action can further improve outcomes for people with multiple myeloma,” he said.
“We welcome the registration of Blenrep and are committed to bringing this innovative therapy to eligible Australians.”
