An experimental pill has achieved complete cancer remission in 18 near-terminal patients with aggressive tumors that have failed to respond to treatments. The disease, acute myeloid leukemia, is the most common blood cancer in adults, with 120,000 cases per year. The three-year survival rate is only 25%. The new drug, called revumenib, has completely eradicated cancer in a third of participants in a highly anticipated clinical trial in the United States. “The results are preliminary and do not suggest a definitive cure, but the authors of the experiment are optimistic. “We think this drug is extremely effective and we hope it will be accessible to anyone who needs it,” says Dr. Ghayas Issa of the University of Texas MD Anderson Cancer Center.
Acute myeloid leukemia affects the bone marrow, where blood cells are produced, causing the uncontrolled production of defective cells. That happened to the 23-year-old Lithuanian architect Algimante Daugliate. She had received two bone marrow transplants from her sister. All other treatments had failed. Her doctors began thinking about palliative care to ease her suffering. “I was desperate. It was like experiencing a terrible movie. I felt like death was imminent, and I was only 21 years old,” she recalls. Two years ago she started taking revumenib pills. She finished university and now works in an architecture studio in Copenhagen.
The drug does not work in all patients. Researchers have focused on two genetic subtypes, in which a protein called menin causes leukemia to develop. Revumenib attaches to the protein and inhibits it thanks to its complex chemical recipe: 32 carbon atoms, 47 hydrogen, one fluoride, six nitrogen, four oxygen and one silver. That formula, C32H47FN6O4S, saved 18 lives. The promising results were published on Wednesday in Nature.
I felt like death was near and I was only 21 years old
Algimante Daugelaite, architect
Haematologist Pau Montesinos, coordinator of the Spanish acute myeloid leukemia group, believes the new information is “quite encouraging,” but she emphasizes caveats: Revumenib still needs to be tested in hundreds of people to confirm its safety and effectiveness . The team from Montesinos, the Leukemia Unit of La Fe Hospital in Valencia, will participate in the next international trials of the pill developed by the US company Syndax Pharmaceuticals.
Montesinos also adds that the drug alone is not a panacea. “In the vast majority of cases, these targeted therapies can reverse leukemia on their own, but rarely cure it,” explains the hematologist. “The strategy is to combine these new drugs with classical chemotherapy or other approaches.” Montesinos recalls the case of another pill, quizartinib, an experimental treatment by Japanese pharmaceutical company Daiichi Sankyo, which inhibits another protein involved in acute myeloid leukemia. Adding quizartinib to chemotherapy increased remission from nearly 40% to nearly 50%, according to preliminary results from a study of 500 patients suffering from another subtype. “For us, an increase in survival of 10 percentage points is a lot,” says the Spanish doctor.
Revumenib’s mechanism of action – the inhibition of the menin protein – is new. Half a dozen pharmaceutical companies are developing substances using the same tactics. The success of Revumenib means good news for them. The oncologist Ghayas Issa calculates that nearly 400,000 people with acute leukemias resistant to other treatments, including myeloid and the most common form of lymphocytes in children, could benefit from the new pills.
These targeted therapies can reverse leukemia on their own, but rarely cure it
Pau Montesinos, haematologist
Issa and his colleagues confirm that economic factors will be key if the pill is approved. According to a report by Democratic Congresswoman Katie Porter, prices of the newest oral cancer drugs in the US are usually above $235,000 per patient.
Revumenib has another weakness, as noted hematologist Eytan Stein of Memorial Sloan Kettering Cancer Center in New York, who led the trials. “The main Achilles’ heel seems to be the development of mutations at the fusion site of the drug, which causes resistance,” explains the researcher. Revumenib had a positive effect on half of the 60 clinical trial participants. However, in some patients, the menin protein changed slightly, causing resistance to the treatment, similar to how bacteria mutate to become antibiotic resistant.
“This shows that we are on the right track and that we are targeting the drug [the menin protein] is critical to the development of leukemia with these genetic subtypes,” says Stein. To avoid such resistance mutations, the authors propose combining drugs with different mechanisms of action. As Ghayas Issa and his colleague Eytan Stein note, menin inhibitors “will certainly play a part part of a treatment for these leukemias.” The architect Algimante Daugelaite celebrates taking part in the process, saying science has given her “another chance to study, work, travel, see the world and most importantly live. “
Sign up for our weekly newsletter to get more English coverage from EL PAÍS USA Edition