An experimental pill achieves complete remission of cancer in 18 patients with very aggressive leukemia

An experimental pill has achieved complete remission of cancer in 18 patients who were practically sentenced to death, due to a very aggressive tumor that did not respond to other treatments.

The disease, acute myeloid leukemia, is the most common blood cancer in adults, with about 120,000 cases per year, and three-year survival barely reaches 25%.

The pill, called revumenib, has achieved complete disappearance of signs of cancer in nearly one in three participants in an anticipated clinical trial in the United States.

The results are preliminary and do not imply a definitive cure, but those responsible for the experiment are optimistic.

“We believe that this drug is extremely effective and we hope that it will be available to all patients who need it,” says Ghayas Issa, M.D.

Acute myeloid leukemia hits the factory of blood cells—the marrow of the bones—and causes the runaway production of faulty cells.

This is what happened to the 23-year-old Lithuanian architect Algimante Daugelaite.

After two bone marrow transplants from her sister and the failure of all treatments, her doctors were already thinking of palliative care to simply alleviate her suffering.

“She was desperate, it was like living a horrible movie.

She felt that death was imminent and she was only 21 years old, ”she recalls.

Exactly two years ago she started taking revumenib pills, she was able to finish her degree and today she works normally in an architecture studio in Copenhagen.

The drug does not work in all cases.

Researchers have focused on two genetic subtypes in which a protein called menin facilitates the progression of leukemia.

Revumenib binds to this protein and inhibits it, thanks to its convoluted chemical recipe: 32 carbon atoms, 47 hydrogen, one fluorine, six nitrogen, four oxygen, and one sulfur.

This formula, C32H47FN6O4S, has so far saved the lives of 18 people.

The promising results are published this Wednesday in the journal

, a benchmark for the best world science.

I felt that death was imminent and I was only 21 years old

Algimante Daugelaite, architect

The hematologist Pau Montesinos, coordinator of the Spanish Acute Myeloid Leukemia Group, believes that the new data is "quite encouraging", but stresses his caution, waiting for revumenib to be tested in hundreds of people and its safety and efficacy confirmed. .

Montesinos' own team, the Leukemia Unit of Hospital La Fe in Valencia, will participate in the upcoming international trials of the pill, developed by the American pharmaceutical company Syndax Pharmaceuticals.

Montesinos stresses that the drug alone is not a panacea.

"In the vast majority of cases, these targeted therapies, by themselves, can reverse leukemia, but hardly cure it," says the hematologist.

“The strategy will be to combine these new drugs with classical chemotherapy drugs or with other approaches”, he believes.

Montesinos recalls the case of another pill, quizartinib, an experimental treatment from the Japanese pharmaceutical company Daiichi Sankyo that inhibits another protein involved in acute myeloid leukemia.

Adding quizartinib to chemotherapy increases cure rates from almost 40% to almost 50%, according to preliminary results from a trial involving half a thousand patients with another genetic subtype.

"For us, raising survival by 10 percentage points is already a lot," celebrates the Spanish doctor.

The mechanism of action of revumenib—inhibition of the menin protein—is novel.

Half a dozen pharmaceutical companies are developing drugs using this same tactic, so the success of revumenib would be good news for the other menin inhibitors.

Oncologist Ghayas Issa estimates that these new pills can benefit almost 400,000 people with acute leukemia resistant to other treatments, both myeloid and the most frequent in children, called lymphocytic.

These targeted therapies alone can reverse leukemia but hardly cure it

Pau Montesinos, hematologist

Issa and his colleagues acknowledge that the economic factor will be key if the pill is finally approved.

The price of the latest oral cancer drugs typically exceeds 200,000 euros per patient per year in the United States, according to a report by Democratic Congresswoman Katie Porter.

Revumenib has one more weakness, admits another of the scientists who led the trials, hematologist Eytan Stein, of the Memorial Sloan Kettering Cancer Center in New York.

“The main Achilles heel seems to be the development of mutations in the binding site of this drug, which generates resistance”, explains the researcher.

Revumenib had some kind of beneficial effect in half of the 60 participants in the clinical trial, but in some of the patients the menin protein changed slightly and resistance to treatment emerged, just like bacteria that mutate and tolerate antibiotics.

“This shows that we are on the right track and that the target of this drug [the menin protein] is critical for the development of leukemia in these genetic subtypes,” says Stein.

To avoid these resistance mutations observed in some patients, the authors propose combining drugs with different mechanisms of action.

In the opinion of Ghayas Issa and his colleague Eytan Stein, menin inhibitors "will definitely be a part of the treatment for these leukaemias."

The architect Algimante Daugelaite is pleased to have participated in the trial and that science has given her “another opportunity to study, work, travel, see the world and, most importantly, live”.

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