Gleevec appears on the cover of TIME magazine

Historical milestone — this page describes an event dated 2001. It is not current breaking news.

A magazine cover, and why it was on time

TIME's issue dated 28 May 2001 carried yellow capsules on the cover under the line "Drugs That Fight Cancer."

The timing was not coincidence. FDA records show that imatinib, sold as Gleevec, received its original approval on 10 May 2001 under application NDA 021335.

A drug reaching a magazine cover is not a medical event. But the science behind it is worth understanding, because it explains what "targeted therapy" actually means, and why the same trick has been hard to repeat.

Forty years of work behind an overnight story

NCI's own account starts in 1960, not 2001.

That year Peter Nowell and David Hungerford examined leukemia cells from two patients with chronic myeloid leukemia and noticed one of the 46 chromosomes was abnormally short. They found the same in seven more patients. It was named the Philadelphia chromosome, after the city. Later work showed 95 percent of CML patients carry it.

At the time, most scientists did not believe cancer was caused by genetic mutations. This was the first evidence that a genetic change could cause a cancer.

In the 1970s, better DNA techniques revealed what the short chromosome was: pieces of chromosomes 9 and 22 break off and swap places. NCI describes the result precisely. The ABL1 gene from chromosome 9 joins the BCR gene on chromosome 22, forming the BCR-ABL1 fusion gene.

Nora Heisterkamp, then at NCI, and colleagues found that fusion. Owen Witte and colleagues at UCLA showed that when it forms in blood cells, it causes CML.

What the fusion gene does, and what the drug does

The fusion gene instructs the bone marrow to make a protein called a tyrosine kinase. That protein is permanently switched on, and it drives too many stem cells to become white blood cells.

In the 1990s Brian Druker set out to find a drug that would block BCR-ABL and leave healthy cells alone, reasoning that normal cells do not have BCR-ABL to block. Working with Nicholas Lydon, he screened a large compound collection.

The compound they found, STI-571, later imatinib, blocks the BCR-ABL protein. Its label also lists it as an inhibitor of the receptor kinases for platelet-derived growth factor and stem cell factor, and of c-Kit.

A phase 1 trial in 1998, partly funded by NCI, made the cancer disappear in most patients with chronic-phase CML. Five years on, 98 percent of those patients were still in remission.

The trial that settled it

The pivotal study, described in the US label, was an open-label, multicenter, international randomized phase 3 trial comparing imatinib against interferon-alpha plus cytarabine.

It randomized 1,106 patients from 177 centers in 16 countries, 553 to each arm. Median age was 51. Imatinib started at 400 milligrams daily.

The primary endpoint was progression-free survival. At 84 months, that was 81.2 percent in the imatinib arm and 60.6 percent with interferon plus cytarabine, with a p-value below 0.0001.

The rate of patients free of progression to accelerated phase or blast crisis at 84 months was 92.5 percent with imatinib against 85.1 percent.

The comparison arm effectively dissolved. Because of crossovers and discontinuation, only 2 percent of patients randomized to interferon were still on that first-line treatment.

The line NCI now writes

NCI states it plainly: someone with CML who is in remission after two years of imatinib treatment has the same life expectancy as someone who does not have cancer.

That sentence is the reason the cover happened. It is also the reason the expectations set that year were unrealistic for most cancers. CML has one driver mutation, present in nearly every case, in a cell type that circulates. Most cancers have nothing so tidy.

When to get checked

CML is quiet, and NCI says so: sometimes it causes no symptoms at all. Many cases turn up on a blood test done for something else.

NCI lists these as reasons to check with a doctor, noting other conditions cause them too:

• Fatigue, meaning feeling very tired.
• Weight loss for no known reason.
• Drenching night sweats.
• Fever.
• Pain or a feeling of fullness below the ribs on the left side.

That last one is the specific one. It usually means an enlarged spleen, and it is the sign least likely to be explained away as stress or a virus.

Diagnosis starts with a complete blood count with differential, then blood chemistry and a bone marrow sample. Our page on chronic myeloid leukemia symptoms covers what those results show.

CML is classified by phase rather than stage: chronic, accelerated, and blastic. In chronic phase, fewer than 10 percent of cells in blood and marrow are blasts. Our page on CML phases explains what changes between them.

The numbers now

The American Cancer Society expects 9,650 new US cases of chronic myeloid leukemia and 1,170 deaths in 2026, and SEER hosts that estimate. Median age at diagnosis, which SEER measures itself, is 67.

Five-year relative survival for 2016 to 2022 cases is 71.1 percent. In 1975 SEER recorded it at about 18 percent.

That change is among the largest in any cancer statistic, and imatinib is the main reason. The figures remain registry averages describing a population rather than a person, and they include people diagnosed at every phase.

What to keep in perspective

A magazine cover is a media event. The science it publicized took four decades and many laboratories.

The "magic bullet" framing set expectations that most cancers could not meet. CML turned out to be unusually well suited to a single-target drug.

Imatinib is not a cure in the ordinary sense for most people. It is a long-term treatment, and resistance can develop, which is why later drugs in the same class exist.

And the numbers here describe groups. Whether any particular treatment fits one person depends on phase, response, and tolerance, decided with a clinician.

Sources

• FDA Drugs@FDA record for NDA 021335 (Gleevec), original approval 10 May 2001, via the openFDA API — https://api.fda.gov/drug/drugsfda.json?search=application_number:%22NDA021335%22&limit=1
• FDA prescribing information for GLEEVEC, via the openFDA drug label API — https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22GLEEVEC%22&limit=1
• NCI, How Gleevec Transformed Leukemia Treatment — https://www.cancer.gov/research/progress/discovery/gleevec
• NCI PDQ, Chronic Myeloid Leukemia Treatment (Patient Version) — https://www.cancer.gov/types/leukemia/patient/cml-treatment-pdq
• TIME magazine cover, Drugs That Fight Cancer, 28 May 2001 — https://content.time.com/time/covers/0,16641,20010528,00.html
• SEER Cancer Stat Facts, Chronic Myeloid Leukemia — https://seer.cancer.gov/statfacts/html/cmyl.html

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.

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