New drug completely cured 18 out of 60 participants of the experiment of aggressive cancer

The experimental pill achieved complete remission of cancer in 18 patients with aggressive, refractory tumors. Read more about this publication English El Pais.

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The most common blood cancer in adults, accounting for 120 cases each year, is acute myeloid leukemia. The survival rate is only 000%. A new drug called revumenib has completely eliminated cancer in a third of participants in a long-awaited US clinical trial. The results are preliminary and do not suggest a definitive cure, but the authors of the experiment are optimistic.

“In our opinion, this medicine is extremely effective. We hope that it will be available to everyone who needs it,” said Dr. Gayas Issa from the Cancer Center. M. D. Anderson University of Texas.

Acute myeloid leukemia affects the bone marrow, where blood cells are made, and causes the uncontrolled production of defective cells. This is exactly what happened to the 23-year-old Lithuanian architect Algimante Daugelate. She received two bone marrow transplants from her sister. Other treatments were unsuccessful. Doctors began to think about palliative care to alleviate her suffering.

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“I was overcome with despair. It was like watching a terrible movie. I felt that death was inevitable, and I was only 21 years old, ”recalls Algimante. She started taking Revumenib two years ago, after which she graduated from college and now works at 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 and inhibits proteins due to its complex chemistry: 32 carbon atoms, 47 hydrogen atoms, one fluoride, six nitrogen atoms, four oxygen atoms and one silver atom. This formula - C32H47FN6O4S - saved 18 lives.

Hematologist Pau Montesinos, coordinator of the Spanish Acute Myeloid Leukemia Group, says the new information is "quite reassuring" but emphasizes that revumenib has yet to be tested in hundreds of people to confirm its safety and effectiveness. The Montesinos team, the Leukemia Unit at La Fe Hospital in Valencia, will take part in the next international trial of a tablet developed by the American company Syndax Pharmaceuticals.

Montesinos says the drug itself is not a panacea.

“In the vast majority of cases, these targeted therapies alone can cure leukemia, but rarely cure it,” explains the hematologist. “The strategy is to combine these new pharmaceuticals with classical chemotherapy or other approaches.”

Montesinos recalls a case involving another pill, quizartinib. It is an experimental drug from Japanese pharmaceutical company Daiichi Sankyo that inhibits another protein involved in acute myeloid leukemia. Adding chemotherapy with quizartinib increased remission from nearly 40% to about 50%, according to preliminary results from a study of 500 patients.

“A 10 percentage point increase in survival is a lot,” says the doctor.

Revumenib's mechanism of action, inhibition of the menin protein, is fairly new. Another 6 pharmaceutical companies are developing substances with the same tactics. The success of revumenib is good news for them. Oncologist Gaias Issa has estimated that the new pills could help nearly 400 people with acute leukemias that are resistant to other treatments, including myeloid and the most common strain in children, called lymphocytic.

Issa and his colleagues agree that economic factors will be key if the pill is approved. Prices for the latest oral cancer drugs typically exceed $235 per patient in the US.

Revumenib has another weakness, as pointed out by hematologist Eitan Stein of Memorial Sloan Kettering Cancer Center in New York, who led the trial.

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“The Achilles heel appears to be the development of mutations when the drug binds to the protein, which causes resistance,” explains the researcher. Revumenib had a positive effect on 30 of the 60 clinical trial participants, 18 of whom were completely cured. In some patients, the menin protein has changed slightly, causing resistance to treatment, just as bacteria mutate to become resistant to antibiotics.

“This suggests that we are on the right track and that the drug's target, the protein menin, is critical for leukemia with these genetic subtypes,” Stein says.

To avoid such resistance mutations, the authors propose to combine drugs with different mechanisms of action. As Gayas Issa and his colleague Eitan Stein note, menin inhibitors “will definitely be part of the treatment for these leukemias.”

Architect Algimante Daugelate is grateful that she participated in the test, because science gave her "another opportunity to study, work, travel, see the world and, most importantly, live."

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