An experimental new drug can make some leukemic cells mature into healthier ones. Illustration by Brian Stauffer

For almost thirty years, William Kuhens worked on Staten Island as a basketball referee for the Catholic Youth Organization and other amateur leagues. At seventy, he was physically fit, taking part in twenty games a month. But in July of 2013 he began to lose weight and feel exhausted; his wife told him he looked pale. He saw his doctor, and tests revealed that his blood contained below-normal numbers of platelets and red and white blood cells; these are critical for, respectively, preventing bleeding, supplying oxygen, and combatting infection. Kuhens was sent to the Memorial Sloan Kettering Cancer Center, in Manhattan, to meet with Eytan Stein, an expert in blood disorders. Stein found that as much as fifteen per cent of Kuhens’s bone marrow was made up of primitive, cancerous blood cells. “Mr. Kuhens was on the cusp of leukemia,” Stein told me recently. “It seemed that his disease was rapidly advancing.”

Leukemia is a disorder of the blood cells, which form in the bone marrow. For reasons not always clear to scientists, immature cells fail to develop properly into mature ones and instead continue to multiply, crowding out normal blood cells. Patients are at risk of massive bleeding and sepsis, a severe complication of infection. There are many kinds of leukemia, depending on the type of blood cell involved and the pace at which the cancer advances. Kuhens was developing acute myelogenous leukemia, or A.M.L., which is estimated to occur annually in at least fifty thousand people worldwide, most of them adults, and is usually lethal; fewer than a quarter of patients survive for more than five years. Kuhens knew that his prognosis was grim, likely measured in months. Stein treated him with four courses of chemotherapy, to no significant effect.

The only options were experimental. Stein had sent a sample of Kuhens’s bone marrow to be analyzed for the presence of thirty or so gene mutations that are known to be associated with blood cancers. The tests revealed one notable mutation, in a gene that produces an enzyme called IDH-2. Normally, the enzyme helps to break down nutrients and generate energy for cells. When mutated, it creates a molecule that alters the cells’ genetic programming. Instead of maturing, the cells remain primitive, proliferate wildly, and wreak havoc.

About fifteen per cent of all A.M.L. patients carry the mutated enzyme. In recent months, Stein had been participating in a Phase 1 clinical trial of a drug, AG-221, designed to target it; the drug was developed by the pharmaceutical company Agios. Phase 1 studies represent the very first tests of a new drug in humans; they are mainly meant to assess a new drug’s safety, with little expectation that the treatment will help. Of the first ten patients who had been treated, three had died from their disease before the drug’s effects could be evaluated. But the data on six of the seven remaining patients were striking: five had gone into complete remission and one entered a partial remission. (The other patient did not improve, and his leukemia continued to grow.)

Stein described one patient to me, a woman in her late sixties with A.M.L. She had already undergone a bone-marrow transplant, had relapsed, and then had more chemotherapy; nothing helped. To Stein’s surprise, after three months on AG-221, her leukemia had gone into complete remission and her blood count had returned to normal. “It was transformative,” Stein said. “She gained weight and told me that the pep in her step was back.” Another patient, a sixty-year-old man with A.M.L., also had failed to benefit from several regimens of chemotherapy, and he, too, went into remission after taking AG-221. Moreover, the side effects of the medication, which is given orally, have been manageable—mostly mild nausea and a loss of appetite.

This past spring, Kuhens entered the drug trial and received his first dose. Within weeks, the leukemic-cell count in his bone marrow had fallen from fifteen per cent to four per cent, and his counts of healthy blood cells improved markedly; he has been in complete remission for four months. The most noticeable side effect has been a metallic taste in his mouth. “For some reason, I can’t stand mayonnaise,” Kuhens told me recently. He just celebrated his fiftieth wedding anniversary. “I want to be around for a while,” he said, “and I don’t know how long this drug will last.”

In April, Stein presented his findings to a packed auditorium at the annual meeting of the American Association for Cancer Research, in San Diego. It was the first public airing of the results of AG-221; patients with progressive A.M.L. had never improved so quickly and definitively.

I received the news with tempered excitement. In the nineteen-seventies, when I trained in internal medicine, and later in hematology and oncology, acute myelogenous leukemia was the cancer to beat. The disease typically overwhelms its victims, relegating them to the intensive-care unit, where they require intravenous antibiotics, blood transfusions, and, as their lungs and heart fail, support on ventilators. The most effective initial treatment was, and still is, a pair of highly toxic chemotherapy drugs, daunorubicin (or sometimes a related one, adriamycin) and cytarabine. The side effects are profound: the first family of drugs causes arrhythmias and heart-muscle damage, often leading to cardiac failure; the second drug is toxic to the central nervous system, particularly the cerebellum, resulting in severe lack of balance and coördination. Combined, the two agents might kill the leukemic cells in the marrow, but they also kill healthy blood cells, causing patients to enter a limbo with an “empty marrow,” during which we doctors used to pray that their normal cells would regrow. Daunorubicin and adriamycin have a distinctive red color, and in my day medical interns referred to them as “the red death,” because most of the patients who took them ultimately died of their disease. In response, my mentors argued that “desperate diseases require desperate measures.”

By comparison, Stein’s results were breathtaking. Still, his trial hadn’t involved many patients, and they hadn’t been followed for long. Cancer is wily, and some drugs that target mutations can show benefits that soon evaporate as the tumor adapts. In June, however, at the European Hematology Association conference, in Milan, Stéphane de Botton, a hematologist at the Institut Gustave Roussy, near Paris, presented updated results that were equally promising. The findings covered thirty-five patients, most of them with A.M.L. Ten had died within a month of entering the trial, from complications related to the disease. But fourteen patients had improved on AG-221, including nine whose leukemia went into complete remission. Five were stable but showed no change; in six, the leukemia continued to grow. The patients also experienced few side effects, de Botton told me recently, and some patients have been in remission for more than six months.

“These data signal the first real advance for A.M.L. in thirty years,” Stephen Nimer, the director of the Sylvester Comprehensive Cancer Center, at the University of Miami, and an eminent leukemia researcher and clinician, told me. “It’s a huge step forward.”

The breakthrough is notable in part for the unconventional manner in which the drug attacks its target. There are many kinds of cancer, but treatments have typically combatted them in one way only: by attempting to destroy the cancerous cells. Surgery aims to remove the entire growth from the body; chemotherapy drugs are toxic to the cancer cells; radiation generates toxic molecules that break up the cancer cells’ DNA and proteins, causing their demise. A more recent approach, immunotherapy, coöpts the body’s immune system into attacking and eradicating the tumor.