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Treatment and the treatment process

Targeted therapy

One of the biggest changes in leukemia treatment over the past twenty years has been the arrival of targeted medicines. Rather than acting on all dividing cells, they aim at a particular “weak spot” in the leukemia cell: an abnormal protein that drives its growth. This topic explains how targeted therapy works, in which leukemias it is used and what to watch out for.

Last updated: ~5 min read
A glowing protein on the surface of a large translucent cell on a dark navy background; a small golden molecule fits into it precisely, like a key.
Figure 1.Concept: the medicine fits its target protein like a key in a lock.

01Short answer

Targeted therapies are medicines that act on specific proteins or signalling pathways that leukemia cells need to survive and grow. These targets are often the result of genetic changes, such as BCR::ABL1 in CML, or FLT3 or IDH mutations in AML. That is why tests check whether the target is present before a targeted medicine is chosen. Many of these medicines are tablets, and some are taken for a long time. They have side effects too, just different ones from chemotherapy.

02Simple explanation

Imagine that inside a leukemia cell there is a broken switch that keeps giving the order “grow, divide!”. A targeted medicine turns that switch off or blocks it.

Chemotherapy acts on all rapidly dividing cells, while targeted medicines act mainly on cells that carry a particular target. So the effect on healthy cells is often smaller, but it does not disappear completely.

Targeted therapy only works if the target is there. That is why the genetic and molecular tests done at diagnosis are so important: they show which medicine is suitable.

The best-known example is CML. Tablets that block the BCR::ABL1 protein have turned this disease, for many people, into a chronic condition that can be controlled for many years.

Targeted medicines can be given alone or together with chemotherapy. Taking tablets regularly, exactly as your doctor prescribed, is very important for treatment to succeed.

03Scientific explanation

The basic idea: according to NCI, targeted therapy acts on proteins that help cancer cells grow, divide and spread. These medicines are mainly of two kinds: small-molecule drugs that can enter the cell, and monoclonal antibodies that attach to targets on the cell surface. Over time, cancer cells can become resistant to these medicines.

CML: in the IRIS trial (2003), the tyrosine kinase inhibitor imatinib gave higher response rates than interferon plus cytarabine in newly diagnosed chronic-phase CML. According to the American Cancer Society, imatinib, dasatinib, nilotinib, bosutinib, ponatinib and asciminib are now used. According to the 2020 ELN recommendations, some people with a long-lasting deep molecular response may try stopping the medicine under strict monitoring conditions (treatment-free remission); this must only be done under medical supervision.

AML and APL: in the RATIFY trial (2017), adding midostaurin to chemotherapy in FLT3-mutated AML improved overall survival. In the VIALE-A trial (2020), adding venetoclax to azacitidine improved survival in people not suited to intensive treatment. In APL, tretinoin (ATRA) and arsenic trioxide make leukemia cells mature; in a 2013 trial this combination was at least as effective as chemotherapy in low- and intermediate-risk APL.

ALL and CLL: according to the American Cancer Society, tyrosine kinase inhibitors are added to treatment for Philadelphia chromosome-positive ALL. In CLL, BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib, pirtobrutinib) and the BCL-2 inhibitor venetoclax are widely used and have replaced chemotherapy in many cases.

04What happens in the body?

How is the target found?

At diagnosis, cytogenetic and molecular tests are run on a bone marrow or blood sample, looking for BCR::ABL1, FLT3, IDH1, IDH2, NPM1 and other changes. Some results are ready within a few days so that a targeted medicine can be added from the start of treatment. At relapse the tests may be repeated, because the genetics of the leukemia can change.

How to take the tablets

Most targeted medicines are taken at home, by you. This is convenient, but it takes responsibility: take the medicine at the same time every day, as your doctor said (with food or on an empty stomach). If you miss a dose, ask your team what to do; do not take two doses together. Do not stop the medicine on your own.

Glowing signal lines inside a cell on a dark navy background; at one point a golden molecule interrupts a line, and beyond it the light dims.
Figure 2.When the target is blocked, the cell’s “grow” signal fades.

Interactions

Some targeted medicines interact with grapefruit, certain antibiotics, antifungal medicines, medicines that reduce stomach acid, and herbal products. This can change the level of the medicine in the blood. Always check with your hematologist or pharmacist before starting any new medicine.

Several translucent tablets floating in soft light on a dark navy background, with calm, healthy-looking blood cells behind them.
Figure 3.Many targeted medicines are taken at home as tablets.

Side effects are different

According to the American Cancer Society, the side effects of targeted medicines depend on the medicine: rashes, diarrhea, changes in liver tests, high blood pressure, heart rhythm changes, swelling or a tendency to bleed. Some medicines can cause differentiation syndrome or tumor lysis syndrome, so close monitoring is needed at the start.

If resistance develops

Sometimes a new mutation appears in the target protein in leukemia cells and the medicine stops working. The doctor can then test for the mutation and switch to another medicine. In CML, for example, some mutations respond only to certain inhibitors. Regular molecular monitoring helps spot this change in time.

05How does a targeted medicine work?

Four steps from the genetic test to monitoring.

Target found — A genetic test reveals the abnormal protein.1Target foundA genetic test reveals the abnormal protein.
Medicine chosen — A medicine matched to that target.2Medicine chosenA medicine matched to that target.
Signal cut — The medicine blocks the protein and growth stops.3Signal cutThe medicine blocks the protein and growth stops.
Monitoring — Molecular tests track the response.4MonitoringMolecular tests track the response.
Genetic targetBCR::ABL1, FLT3, IDH, BTK, BCL-2.
TabletsMostly at home, taken regularly.
Molecular responseTracked by PCR.

06Targets and example medicines in leukemia (simplified)

TargetExample medicinesWhere used
BCR::ABL1Imatinib, dasatinib, nilotinib, bosutinib, ponatinib, asciminibCML, Philadelphia-positive ALL
FLT3Midostaurin, gilteritinib, quizartinibFLT3-mutated AML
IDH1 / IDH2Ivosidenib, olutasidenib / enasidenibIDH-mutated AML
BCL-2VenetoclaxAML (with azacitidine or decitabine), CLL
BTKIbrutinib, acalabrutinib, zanubrutinib, pirtobrutinibCLL
PML::RARATretinoin (ATRA), arsenic trioxideAPL
MeninNewer medicines such as revumenibAcute leukemias with certain genetic changes

* This table is not complete, and approved medicines differ from country to country. Which medicine suits you is decided only by your hematology team, based on your test results.

07Key terms

Targeted therapy
A medicine acting on a specific protein or signalling pathway in the leukemia cell.
Tyrosine kinase inhibitor
A medicine that blocks kinase enzymes that pass on the “grow” signal.
BCR::ABL1
The fusion gene created by the Philadelphia chromosome in CML.
FLT3
A growth-receptor gene often mutated in AML.
IDH1 / IDH2
Enzyme genes whose mutation disrupts cell maturation.
BCL-2
A protein that prevents cells from dying.
BTK
A signalling protein important for B-lymphocyte survival.
Differentiation syndrome
A serious reaction when leukemia cells mature rapidly.
Treatment-free remission
Remission in CML that continues after stopping the medicine under strict monitoring.
Resistance
When leukemia no longer responds to a medicine, often because of a new mutation.

08Key points

  • Targeted medicines block a specific protein in the leukemia cell.
  • They only work if the target is present.
  • Genetic and molecular tests reveal the target.
  • In CML, tablets keep the disease under control for a long time.
  • There are targeted medicines for AML, APL, ALL and CLL too.
  • Taking tablets regularly and correctly is important.
  • Because of interactions, clear new medicines with your doctor.
  • Side effects differ from chemotherapy, but they do happen.

09Frequently asked questions

Is targeted therapy better than chemotherapy?

Neither better nor worse, just different. In some leukemias targeted medicines are the main treatment, in others they are added to chemotherapy, and in others there is no suitable target. Your hematologist chooses the approach that suits you best.

How long will I need to take the tablets?

It depends on the medicine and the leukemia. In CML it is often for years; in other cases it is for a set period. Only your doctor decides how long.

I feel well. Can I stop the medicine?

No, do not stop without talking to your doctor. Feeling well does not mean the leukemia has gone. In CML, stopping is possible only under special conditions and with strict monitoring.

What should I do if I forget a dose?

Follow the instructions your team gave for your medicine. As a general rule, do not take two doses together to “make up” for a missed one. If in doubt, call your pharmacist or nurse.

Do targeted medicines cause hair loss?

Usually there is not the heavy hair loss seen with chemotherapy, but some medicines can cause hair thinning or skin changes. Each medicine has its own side effect profile.

Can I become pregnant during targeted therapy?

Many targeted medicines can be harmful to a developing baby. Be sure to discuss reliable contraception and any pregnancy plans with your hematologist.

10Questions for your doctor

Take these questions to your appointment. The ones you save are collected on the “My questions” page and stay on this device only.

  1. Is a targeted drug suitable for me, and why?

  2. How and when should I take it?

  3. Which foods and medicines may interact with it?

  4. How will we know the drug is working?

My questions

12Sources

  1. National Cancer Institute (NCI). Targeted Therapy for Cancer
  2. National Cancer Institute (NCI). Drugs Approved for Leukemia
  3. National Cancer Institute (NCI). Chronic Myeloid Leukemia Treatment (PDQ®) — Patient Version
  4. American Cancer Society. Targeted Therapy
  5. American Cancer Society. Targeted Drug Therapy Side Effects
  6. American Cancer Society. Targeted Therapy Drugs for Acute Myeloid Leukemia (AML)
  7. American Cancer Society. Targeted Therapy Drugs for Acute Lymphocytic Leukemia
  8. American Cancer Society. Targeted Therapy Drugs for CML
  9. American Cancer Society. Targeted Therapy Drugs for CLL
  10. Leukemia, 2020. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia
  11. Blood (American Society of Hematology), 2022. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN
  12. New England Journal of Medicine, 2003. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia
  13. New England Journal of Medicine, 2013. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia
  14. New England Journal of Medicine, 2017. Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation
  15. New England Journal of Medicine, 2020. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia
Medical disclaimerThis information is for educational purposes only and does not replace medical advice.
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