The Pill That Could

Chapter 10: What Cure Means

Bud Romine, the Oregon truck driver from chapter six, took imatinib for nearly twenty years.

He had enrolled in the phase 1 trial in 1998, in late-stage CML, with what he had been told was perhaps months to live. He started on a higher dose cohort. His blood counts came down. His bone marrow improved. He went back to driving. He sent postcards. Through the early and middle 2000s he was, by every measure his oncologist could apply, doing well — the disease was in deep cytogenetic and then molecular response, his blood counts were stable, his Philadelphia chromosome was undetectable on karyotyping. He continued on imatinib because, by every account he received from his oncologist and from the protocols of the trial he had stayed on, that was what you did with imatinib in CML. You stayed on it. You kept taking it. Your disease, in the language oncologists had begun to use, was being managed.

Romine eventually developed an unrelated cancer in his late seventies. He died of complications related to that cancer in 2017, having outlived by roughly nineteen years the prognosis he had been given when he enrolled in Druker's trial. The CML had not killed him. The CML, on every test that had been done in the years before his death, had remained suppressed.

Was Romine cured?

It is a question that depends on what ‘cured’ means, and the answer that took the field most of the 2000s and 2010s to arrive at, and that is still being refined in 2026, is: not exactly, but maybe close enough that the distinction is, for him and most patients like him, not the question that matters.

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What ‘cure’ has historically meant in oncology is straightforward in concept and complicated in practice.

The conceptual definition is: the cancer is gone, and it stays gone, and the patient eventually dies of something else. The biological criterion is the absence of any remaining cancer cell anywhere in the body — zero, not few. A cancer that has been removed by surgery and that does not recur after many years of follow-up, in a patient who shows no evidence of disease anywhere on imaging or in blood work, is generally called cured. So is a leukemia in long-term remission after a successful bone marrow transplant. So is, by tradition, a tumor whose response to chemotherapy is so complete and so durable that the cancer never reappears for the rest of the patient's life.

The practical difficulty is that you can never quite prove the absence of cancer. Cancer cells are small; the body is big; the most sensitive tests can detect cancer down to some threshold of frequency, below which the cells become invisible to the test. A patient declared cured of breast cancer, with clean scans and clean blood, may still have a small population of dormant cancer cells somewhere in her bone marrow that no test has found. Most of the time, in such a patient, those cells will remain dormant for the rest of her life. Sometimes, decades after the original treatment, they will reactivate, and the cancer will return — a recurrence after what had looked, by every available measure, like a complete cure. The biological question ’are there any cancer cells left' is harder to answer in any specific patient than the medical question ’has the cancer recurred,' which is what oncologists actually track.

The way oncology has historically managed this difficulty is through a combination of follow-up and statistics. Patients are followed; recurrences are counted; survival curves are plotted. A treatment is said to cure when, after enough years, the survival curve flattens out — when the rate of new recurrences drops to roughly the background mortality rate of the population, suggesting that the patients still alive are no more likely to die of the cancer than they are to die of the other things people eventually die of. Cure, on this definition, is something you can establish at the level of a population without ever being entirely sure about any one patient. It is also something that takes a long time to establish, because you need many patients followed for many years to be confident the curve has actually flattened.

CML in the imatinib era poses a different problem. Imatinib doesn't, in most patients, eliminate the disease the way successful chemotherapy or transplant does in some other leukemias. It suppresses the disease, sometimes very deeply, sometimes to levels too low for any clinical test to detect, but the suppression is contingent on the drug. Stop the drug, in most patients, and the disease comes back. The traditional definition of cure — cancer gone, stays gone, no further treatment needed — doesn't fit. What does fit is something the field had to develop new vocabulary for.

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The new vocabulary built up over the 2000s as the long-term data on imatinib began to accumulate. The most consequential single piece of that data came from a trial called IRIS.

IRIS — the International Randomized Study of Interferon and STI571 — was the phase 3 trial Novartis had committed to running as part of its accelerated-approval agreement. It enrolled, beginning in mid-2000, more than a thousand newly diagnosed chronic-phase CML patients across many sites in many countries, randomized them between imatinib and the previous standard of care (interferon plus low-dose cytarabine), and followed them for outcomes that mattered: cytogenetic response, molecular response, progression to advanced disease, overall survival.

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