Experimental pill achieves complete cancer remission in 18 people with aggressive leukemia | science and technology

An experimental pill achieved complete cancer remission in 18 terminally ill patients with aggressive tumors that failed to respond to treatment. The disease, acute myeloid leukemia, is the most common blood cancer in adults, with 120,000 cases each year. The three-year survival rate is only 25%. The new drug, called revumenib, completely eliminated cancer in a third of participants in a long-awaited clinical study in the United States. “The results are preliminary and do not suggest a definitive cure, but the authors of the experiment are optimistic. “We believe this drug is extraordinarily effective and we hope it will be available to everyone who needs it,” says Dr. Ghayas Issa of the University of Texas MD Anderson Cancer Center.

Acute myeloid leukemia attacks the bone marrow, where blood cells are produced, and causes the uncontrolled production of defective cells. This is what happened to 23-year-old Lithuanian architect Algimante Daugeliate. She had received two bone marrow transplants from her sister. All other treatments had failed. His doctors had started thinking about palliative care to relieve his suffering. “I was desperate. It was like living in a horrible movie. I felt like death was imminent and I was only 21,” 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 for all patients. The researchers focused on two genetic subtypes, in which a protein called menin allows leukemia to progress. Revumenib attaches to the protein and inhibits it, thanks to its complex chemical recipe: 32 carbon atoms, 47 hydrogen, one fluorine, six nitrogen, four oxygen and one silver. This formula, C32H47FN6O4S, saved 18 lives. The promising results were published Wednesday in Nature.

I felt like death was imminent and I was only 21

Algimante Daugelaite, architect

Hematologist Pau Montesinos, coordinator of Spain’s acute myeloid leukemia group, says the new information is “pretty optimistic”, but she stresses the caveats: revumenib still needs to be tested in hundreds of people to confirm its effectiveness. safety and efficacy. The team from Montesinos, the leukemia unit of La Fe hospital in Valencia, will take part in the next international trials of the pill, developed by the American company Syndax Pharmaceuticals.

Montesinos also adds that the drug alone is not a panacea. “In the vast majority of cases, these targeted therapies, on their own, can reverse leukemia, but rarely cure it,” explains the hematologist. “The strategy is to combine these new pharmaceuticals with conventional chemotherapy or other approaches.” Montesinos recalls the case of another pill, quizartinib, an experimental treatment from the Japanese pharmaceutical company Daiichi Sankyo, which inhibits another protein implicated in acute myeloid leukemia. Adding quizartinib to chemotherapy increased remission from almost 40% to almost 50%, according to preliminary results from a trial of 500 patients with another subtype. “For us, increasing survival by 10 percentage points is a lot,” says the Spanish doctor.

Revumenib’s mechanism of action, inhibition of the protein menin, is novel. Half a dozen pharmaceutical companies are developing substances with the same tactic. The success of Revumenib means good news for them. Oncologist Ghayas Issa calculates that the new pills could benefit nearly 400,000 people with acute leukemia resistant to other treatments, including myeloid and the most common strain in children, called lymphocytic.

These targeted therapies alone can reverse leukemia, but rarely cure it

Pau Montesinos, hematologist

Issa and his colleagues say economic factors will drive whether the pill is approved. Prices for the latest oral cancer pharmaceuticals tend to exceed $235,000 per patient in the United States, according to a report by Democratic Congresswoman Katie Porter.

Revumenib has another weak point, as pointed out by hematologist Eytan Stein of Memorial Sloan Kettering Cancer Center in New York, who led the trials. “The main Achilles’ heel appears to be the development of mutations at the drug’s fusion site, which leads to resistance,” explains the researcher. Revumenib had a positive effect on half of the 60 clinical trial participants. In some patients, however, the menin protein changed slightly, causing resistance to treatment, similar to how bacteria mutate to become resistant to antibiotics.

“It demonstrates that we are on the right track and that the target of the drug [the menin protein] is essential for the development of leukemia with these genetic subtypes,” Stein says. To avoid such resistance mutations, the authors propose combining drugs with different mechanisms of action. As Ghayas Issa and his colleague Eytan Stein observe, menin inhibitors “will certainly be part of a treatment for these leukaemias”. Architect Algimante Daugelaite celebrates his participation in the trial, saying that science has given him “another opportunity to study, to work, to travel, to see the world and, above all, to live”.

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