Key points
- Not everyone with CLL is treated straight away. While the disease is quiet, only regular tests and check-ups are needed; starting treatment earlier does not lengthen life [1].
- When treatment is needed, the first treatment for most patients today is targeted tablets, not chemotherapy [2].
- There are two main approaches: a daily tablet taken continuously, or a course of about a year that then stops [2, 7, 8].
- Two gene tests (TP53 and IGHV) are needed before treatment; their results change the choice of drug [2].
What is CLL, and why is not everyone treated straight away?
Chronic lymphocytic leukaemia (CLL) is a slow cancer of white blood cells called lymphocytes. Many patients find out by chance, on a routine blood test, and have no symptoms for years.
That is why doctors do not give treatment at this stage and simply keep an eye on the disease; studies have shown that starting treatment before the disease "becomes active" does not lengthen life [1]. This "watch and wait" is not neglect; it is itself part of the right treatment.
When is treatment needed?
Treatment starts when the disease becomes active; for example [1]:
- Anaemia or falling platelets that are getting worse
- Large or troublesome lymph nodes or spleen
- A rapid rise in lymphocytes (doubling in less than 6 months)
- Fever, night sweats or unexplained weight loss
Recognising this point is for your haematologist; do not skip your regular tests.
How treatment has moved on
Until about ten years ago, the best treatment for CLL in fit patients was a combination of chemotherapy and an antibody called FCR; in its time it was a big step forward and lengthened patients' lives [11]. But it was hard going and caused more infections and low blood counts [11].
Then targeted tablets arrived and did better in head-to-head comparisons: in patients aged 70 or younger, ibrutinib tablets with an antibody lengthened life more than FCR and halved serious infections [3, 4]; in older people too, the tablets controlled the disease far better than chemotherapy [5, 6]. Read the full story of this change in Chemotherapy or targeted tablets in CLL?
Today's options
A daily tablet taken continuously
Tablets such as ibrutinib (and its next generation, acalabrutinib and zanubrutinib) are taken every day for as long as they work. In older people, four years on, the disease had stayed quiet in most of those taking the tablet; far more than with chemotherapy [6]. The second generation of these tablets has fewer heart side effects [12, 2].
A year of treatment, then stop
Venetoclax tablets with an antibody, for only about a year. In patients who also had other illnesses, the disease usually stayed quiet for more than 6 years after this one year of treatment; nearly twice as long as with the old treatment [7].
Two tablets together, for a fixed time
Ibrutinib and venetoclax together, for about 15 months. Three and a half years later, the disease was quiet in most patients; with chemotherapy, in only a quarter [8]. Acalabrutinib with venetoclax was also better than chemotherapy [9].
Length of treatment guided by a very sensitive test
A very precise blood test shows how much disease is left and how long treatment should continue. With this approach, five years on, the disease was quiet in almost everyone; far better than with chemotherapy [10].
Which is best for me?
The 2026 European guideline has these messages [2]:
- Before any treatment, test for TP53 (and before the first treatment, IGHV).
- For most patients without a TP53 change, fixed-duration treatment is preferred to taking a drug indefinitely.
- If a continuous tablet is needed, the second generation (acalabrutinib or zanubrutinib) is preferred because of fewer side effects.
- Vaccines (pneumococcus, shingles, flu, COVID-19 and hepatitis B) are recommended.
Heart and kidney disease, your other medicines and whether you prefer to stop or keep taking a drug all matter in the choice.
Ask your doctor before treatment starts
When should I call my doctor?
Tell your doctor early about fever or infection, unusual bruising or bleeding, a racing heart or dizziness (especially with tablets such as ibrutinib), and rapidly growing lymph nodes [4, 6]. If you are starting venetoclax, have the tests in the first days exactly on time (venetoclax).
Frequently asked questions
Can CLL be cured?
Usually the aim is long-term control rather than cure; but today many patients live normal lives for years with controlled disease. For example, with a year of venetoclax treatment the disease usually stayed quiet for more than 6 years [7].
Will I have to take tablets for the rest of my life?
Is chemotherapy still used in CLL?
For physicians
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Indication for treatment: iwCLL 2018 (active disease); early treatment of asymptomatic disease gives no survival benefit [1]. TP53 (del17p and mutation) before every line of treatment and IGHV before first line [2].
First-line evidence: E1912 (age 70 or under): IR versus FCR, 3-year OS 98.8% versus 91.5% (HR 0.17), grade ≥3 infection 10.5% versus 20.3% [3]; 5.8-year follow-up OS HR 0.47 [4]. RESONATE-2 (age 65 and over): ibrutinib versus chlorambucil, HR for progression 0.16 [5]. A041202: 4-year PFS 76% versus 47% with BR [6]. CLL14: VenO median PFS 76.2 versus 36.4 months [7]. GLOW: I+V versus Clb-O, 42-month PFS 74.6% versus 24.8% [8]. AMPLIFY: AV versus FCR/BR, 36-month PFS 76.5% versus 66.5% [9]. FLAIR: MRD-guided I+V, 5-year PFS 93.9% versus 58.1% with FCR (HR 0.13) [10]. ALPINE: zanubrutinib versus ibrutinib in relapsed CLL, better PFS and fewer cardiac events [12].
EHA 2026: in patients without a TP53 abnormality, fixed-duration regimens are preferred; if a continuous BTKi is needed, second generation [2]. Doses: CLL regimens on the leukaemia page.
Scientific evidence
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Scientific evidence
9 itemsiwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL
EHA Guidelines on management of chronic lymphocytic leukemia and Richter transformation
Long-term outcomes for ibrutinib-rituximab and chemoimmunotherapy in CLL: updated results of the E1912 trial
Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia
Follow-up from the A041202 study shows continued efficacy of ibrutinib regimens for older adults with CLL
Fixed-duration ibrutinib-venetoclax versus chlorambucil-obinutuzumab in previously untreated chronic lymphocytic leukaemia (GLOW): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial
Measurable Residual Disease-Guided Therapy for Chronic Lymphocytic Leukemia
Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized phase 3 CLL14 study
Fixed-Duration Acalabrutinib Combinations in Untreated Chronic Lymphocytic Leukemia
Read more
Related cancer types
Treatment guides
References
12 referencesShow all references, 12 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
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- 9Fixed-Duration Acalabrutinib Combinations in Untreated Chronic Lymphocytic Leukemia
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- 11Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial
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This page is based on reputable scientific sources and was last updated on 28 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.
Printed from the website; the full and up-to-date version: https://drdabiri.com/en/articles/best-treatment-cll/
