Patients with terminal leukemia who do not respond to treatment now have hope for a cure, thanks to a new experimental pill called revumenib.
This drug completely eliminated cancer in a third of the participants in a long-awaited clinical trial in the United States.
Although not all patients showed complete remission, scientists remain hopeful because the results indicate that the pill may pave the way to a cure for leukemia in the future.
“We are incredibly hopeful about these results of the patients who received this drug. This is their last chance,” said study co-author Dr Ghayas Issa, a leukemia physician at MD Anderson. Cancer Center at the University of Texas.
“They progressed through multiple lines of therapy and a fraction of them, about half, lost their leukemia cells from their bone marrow,” he told Euronews Next.
How does this pill work?
Acute myeloid leukemia (AML) is a type of cancer that attacks the bone marrow, where blood cells are made, and causes the uncontrolled production of defective cells.
Revumenib is a new class of targeted therapy for chronic leukemia that inhibits a specific protein called menin. The drug works by reprogramming leukemia cells back into normal cells.
Menin is involved in the complex machinery that is hijacked by leukemia cells and causes normal blood cells to become cancerous.
By using revumenib, Issa explained, the machine is turned off and the leukemia cells are returned to normal cells, resulting in remission.
This formula has already saved 18 lives as part of a clinical trial, with promising results published this month in Nature.
Preliminary results showed that 53 percent of patients responded to revumenib, and 30 percent had a complete remission with no cancer visible in their blood.
Based on data from this trial, in December 2022, the US Food and Drug Administration granted revumenib “breakthrough therapy designation” to help fast-track its development and regulatory review.
A cure for leukemia, but not for everyone
“This is certainly a breakthrough and it is a result of years of science. Many groups have worked hard in the lab to understand what causes these leukemias,” said Issa.
However, he explained that the drug does not work for all patients. This is for a specific subset of leukemia that usually has missing or mislabeled genes or a chromosome fusion.
The experimental pill targets the most common mutation in acute myeloid leukemia, a gene called NPM1, and a less common fusion called KMT2A. Combined, these mutations are estimated to occur in about 30 to 40 percent of people with acute myeloid leukemia.
The phase 1 trial enrolled 68 patients at nine US hospitals. All of them saw their leukemia come back after other treatments or never responded well to traditional chemotherapy drugs in the first place.
Among them is Algimante Daugeliate, a 23-year-old Lithuanian architect who was diagnosed with leukemia. He received two bone marrow transplants from his brother, but all other treatments failed. His doctors even considered palliative care to ease his suffering.
“I’m desperate. It’s like I’m living in a horror movie. I feel like death is imminent, and I’m only 21 years old,” she said El Pais.
However, once she started taking revumenib two years ago, Daugeliat made a full recovery. Since then, he has been able to resume his normal life, graduating from college and working in an architecture studio in Copenhagen.
Strong effect for limited effect
According to Issa, although this drug is relatively safe compared to standard treatments for leukemia, two main side effects have been identified.
The first affects the heart’s electrical system and can be determined using an electrocardiogram (ECG). However, reducing the dose or stopping the treatment resolved the issue in all cases, Issa said.
The second side effect is referred to as differentiation syndrome – a group of potentials life-threatening reactions in blood cancer treatments – but it can be managed effectively if it is recognized early and appropriate steps are taken to stop it. According to Issa, all cases of differentiation syndrome in this study were successfully managed without any complications for the patients.
The study is still in its early stages and the results remain preliminary. Phase I studies like this one aim to test whether a drug is safe and to find the highest dose that can be given to them without causing serious side effects.
A phase II study looking specifically at the effectiveness of revumenib is now underway.
Twelve patients in the trial who responded to the drug went on to receive a stem cell or bone marrow transplant. Such transplants require that patients have no cancer or only a very low level of cancer in their blood – and revumenib helps them get there.
While the experimental pill is not a sure cure, the researchers who worked on the trial are optimistic.
“In the future, we plan to combine this pill with the standard treatments we currently have for acute leukemias,” Issa said.
“That’s the most likely strategy to get us to cures where patients don’t need to see leukemia doctors anymore and don’t need treatments for leukemia anymore”.