Experimental pill achieves complete cancer remission in 18 people with aggressive leukemia

An experimental pill has achieved the complete remission of cancer in 18 near-terminal patients with aggressive tumors that did not respond to treatments. The illness, acute myeloid leukemia, is the most common blood cancer in adults, accounting for 120,000 cases each year. The three-year survival rate is just 25%. The new drug, called revumenib, has completely eliminated cancer in a third of the 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 think this pharmaceutical is extraordinarily effective, and we hope for it to be accessible to everyone who needs it,” says Dr. Ghayas Issa from the MD Anderson Cancer Center at the University of Texas.

Acute myeloid leukemia attacks bone marrow, where blood cells are produced, and causes the uncontrolled production of defective cells. That’s what happened to the 23-year-old Lithuanian architect Algimante Daugeliate. She had received two bone marrow transplants from her sister. All other treatments had failed. Her doctors had begun thinking about palliative care to alleviate her suffering. “I was desperate. It was like living through a horrible movie. I felt like death was imminent, and I was just 21 years old,” she recalls. Two years ago, she started to take revumenib pills. She finished college, and now she works at an architecture studio in Copenhagen.

The drug does not work for all patients. Researchers have 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 of hydrogen, one fluoride, six nitrogen, four oxygen and one of silver. That formula, C32H47FN6O4S, has saved 18 lives. The promising results were published on Wednesday in Nature.

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

Algimante Daugelaite, architect

Hematologist Pau Montesinos, coordinator of the Spanish Group of Acute Myeloid Leukemia, believes that the new information is “fairly hopeful,” but she emphasizes the caveats: revumenib still must be tested on hundreds of people to confirm its safety and effectiveness. Montesinos’s team, the Leukemia Unit at the La Fe hospital in Valencia, will participate in the next international trials of the pill, developed by the American company Syndax Pharmaceuticals.

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

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

These targeted therapies, on their own, can revert leukemia, but rarely cure it

Pau Montesinos, hematologist

Issa and his colleagues agree that economic factors will be key if the pill is approved. The prices of the latest oral pharmaceuticals against cancer tend to be over $235,000 per patient in the US, according to a report by Democratic congressperson Katie Porter.

Revumenib has one other weak point, as pointed out by hematologist Eytan Stein of the 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 drug’s fusion site, which causes resistance,” the researcher explains. Revumenib had some positive effect on half of the 60 participants in the clinical trial. In some of the patients, though, the menin protein changed slightly, causing resistance to the treatment, similar to how bacteria mutate to become antibiotic-resistant.

“This demonstrates that we’re on the right path, and that the target of the drug [the menin protein] is critical for the development of leukemia with these genetic subtypes,” Stein says. To avoid such resistance mutations, the authors propose combining pharmaceuticals with different mechanisms of action. As Ghayas Issa and his colleague Eytan Stein observe, menin inhibitors “will definitely be part of a treatment for these leukemias.” The architect Algimante Daugelaite is grateful that she was part of the trial, saying that science has given her “another opportunity to study, work, travel, see the world, and, most importantly, live.”

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