A new type of cancer therapy has produced dramatic results in patients with advanced leukaemia in an early-phase clinical trial...
A new type of cancer therapy has produced dramatic results in patients with advanced leukaemia in an early-phase clinical trial, scientists say.
Approximately 15 per cent of acute myeloid leukaemia patients have a mutated form of the IDH2 gene. IDH2 normally makes a protein that plays a critical role in cell metabolism.
However, when the gene is mutated, it leads to an increase in production of 2-hydroxyglutarate, which prevents immature white blood cells from developing into healthy, infection-fighting cells.
These immature cells accumulate, crowd out normal cells, and lead to the development of acute leukaemia.
AG-221 is an investigational drug that blocks the mutated IDH2 protein, effectively allowing these immature white blood cells to develop normally.
“Traditional forms of cancer therapy â€” surgery, chemotherapy, and radiation â€” work by killing cancer cells,” said Eytan M Stein, a medical oncologist at Memorial Sloan Kettering Cancer Centre in New York, US.
“But they have major side effects since healthy cells are often also affected. Targeted therapies are much more precise,” said Stein, who led the study.
“AG-221 is especially unique. Instead of inhibiting a mutation that leads to cancer cell growth, it works by targeting a gene that can transform cells into becoming healthy again,” he added.
As part of the study, 45 patients with IDH2-positive leukaemia or haematologic malignancies were able to complete one cycle of therapy and were evaluated for efficacy.
All patients had advanced disease that had relapsed or was unresponsive to prior therapy.
Patients received up to 150mg or 200mg of AG-221 once or twice daily in 28-day cycles; the maximum tolerated dose has not yet been reached.
The overall response rate was 56 per cent; 15 patients (33 per cent) achieved complete remission and 10 patients (22 per cent) partial remission.
In addition, 17 patients (38 per cent) achieved stable disease. Further, responses have been durable, including complete remissions that have lasted up to eight months and are ongoing. There were no treatment-related deaths.
“This drug has the potential to transform the treatment of leukaemia,” said Stein.
“We haven’t yet reached the maximum tolerated dose and patients are responding dramatically. More research is needed, but I am optimistic that this drug will fundamentally alter the natural history of IDH2-mutant leukaemia and other haematologic malignancies,” Stein said.