Imatinib transforms chronic myeloid leukemia

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

One broken join, one drug

Chronic myeloid leukemia has an unusually simple cause, and that simplicity is why it became the proving ground for targeted cancer treatment.

NCI describes it this way. In CML, a piece of DNA from one chromosome moves to another. Pieces of chromosomes 9 and 22 break off and swap places. The ABL1 gene from chromosome 9 lands next to the BCR gene on chromosome 22 and fuses with it. The altered chromosome 22 is called the Philadelphia chromosome.

The fused BCR::ABL1 gene makes a tyrosine kinase, an enzyme that relays growth signals. This one is stuck on. The bone marrow keeps turning stem cells into white blood cells that nobody asked for. NCI notes the Philadelphia chromosome is not inherited from a parent.

One fault. One protein. One thing to block.

The approval

On 10 May 2001 the FDA approved imatinib, sold as Gleevec, under NDA 021335 from Novartis. It was classified as a new molecular entity. Two further efficacy supplements followed in 2002.

Imatinib was built to sit in the pocket of the BCR-ABL kinase and stop it working. It was among the first drugs designed against a specific molecular fault rather than found by testing chemicals against dividing cells. Our overview of targeted therapy traces what that shift meant for the drugs that followed.

What eleven years showed

The IRIS trial randomized people with newly diagnosed chronic-phase CML to imatinib or to interferon alfa plus cytarabine, the previous standard. Long-term results were published in the New England Journal of Medicine in 2017.

Two things about the design matter. It was open-label, and it allowed crossover. In practice 65.6% of those assigned to interferon plus cytarabine crossed over to imatinib, after a median of only 0.8 years. So the long-term analysis focuses on the imatinib group rather than comparing the two arms.

With a median follow-up of 10.9 years, the estimated overall survival at 10 years in the imatinib group was 83.3%. Complete cytogenetic response, meaning no cells carrying the Philadelphia chromosome could be found, was achieved by 82.8%. About half, 48.3%, completed study treatment on imatinib.

Serious side effects attributed to imatinib were uncommon and clustered in the first year. The authors concluded that long-term use was not associated with unacceptable cumulative or late toxicity.

What that meant in practice

Before imatinib, chronic-phase CML was managed with interferon, and the definitive option was an allogeneic stem cell transplant, which carries real mortality of its own. Our page on stem cell transplant explains what that procedure involves.

After imatinib, most people with chronic-phase CML take a daily tablet and are monitored with blood tests. That is a different kind of life. It is also a different kind of problem: adherence, side effect management over decades, and cost become the issues rather than survival to five years.

Where CML sits now

The count of 9,650 new US chronic myeloid leukemia diagnoses and 1,170 deaths in 2026 is an American Cancer Society projection, listed on SEER's site. What SEER measures itself is survival: 71.1% at five years, for cases diagnosed in 2016 to 2022.

That figure covers everyone diagnosed, at every age and phase, including people diagnosed in accelerated phase or blast crisis where the disease behaves very differently. It is a group statistic over past years and does not describe any individual's course. Our page on chronic myeloid leukemia goes into the phases.

When to get checked

NCI notes that CML sometimes causes no symptoms at all, and is often found on a routine blood count. When there are symptoms, it lists:

• Fatigue that does not lift with rest
• Weight loss with no known cause
• Drenching night sweats, the kind that soak bedding
• Fever
• Pain or a feeling of fullness below the ribs on the left side, where the spleen sits

Any of these lasting more than two to three weeks is worth a blood count. Diagnosis is confirmed with cytogenetic analysis, which examines chromosomes in a bone marrow or blood sample, or FISH testing, which uses fluorescent DNA probes to count specific genes.

What this does not mean

• IRIS studied newly diagnosed chronic-phase CML. Accelerated phase and blast crisis are different situations with different outcomes.
• Because most of the comparison group crossed over within a year, the long-term data describe the imatinib group rather than proving a head-to-head margin over interferon.
• Imatinib does not work everywhere. Its success rests on one specific fusion gene, and most cancers have no such single switch.
• Second and third-generation inhibitors have since arrived, and resistance mutations are a known problem. Imatinib is a starting point in CML care, not the end of it.
• The 83.3% ten-year figure comes from a selected trial population, followed under trial conditions.

Sources

• FDA Drugs@FDA (openFDA API), GLEEVEC NDA 021335, original approval 10 May 2001 — https://api.fda.gov/drug/drugsfda.json?search=application_number:%22NDA021335%22
• New England Journal of Medicine (record via PubMed), Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia — https://pubmed.ncbi.nlm.nih.gov/28273028/
• NCI PDQ, Chronic Myeloid Leukemia Treatment (Patient Version) — https://www.cancer.gov/types/leukemia/patient/cml-treatment-pdq
• NCI, Imatinib Mesylate — https://www.cancer.gov/about-cancer/treatment/drugs/imatinibmesylate
• 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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