EHA Guidelines on management of chronic lymphocytic leukemia and Richter transformation
- Study type
- Clinical guideline
- Study name
- EHA CLL 2026
- Design
- Evidence-based clinical guideline of the European Hematology Association (EHA), with levels of evidence and grades of recommendation and the participation of patient representatives
- Source
- HemaSphere · 2026
In plain words
This is the latest European guideline for CLL. Its main messages: treatment should start only when the disease is active; before any treatment, genetic tests for TP53 and (before the first treatment) IGHV should be done; for most patients without a TP53 abnormality, fixed-duration targeted treatments (for example one year) are preferred over taking a drug indefinitely; and if continuous treatment with a BTK inhibitor is needed, second-generation drugs (acalabrutinib or zanubrutinib) are preferred because they cause fewer side effects. Vaccination (pneumococcus, shingles, hepatitis B, flu and COVID) is also recommended.
Key guideline recommendations
- I, A
Treatment should be started only when iwCLL criteria are met.
- II, B
The somatic mutation status of the IGHV genes should be determined in all patients with CLL before first-line treatment.
- II, B
TP53 abnormalities (17p deletion by FISH and TP53 gene mutations by NGS) should be assessed in all patients before every line of treatment.
- I, A
In patients without a TP53 abnormality, fixed-duration targeted treatments are preferred over continuous treatment.
- I, A
For continuous treatment in all new patients, acalabrutinib and zanubrutinib are preferred over ibrutinib because of their more favourable adverse event profile; patients well controlled on ibrutinib without significant adverse events should not be switched.
- I, A
In patients with a TP53 abnormality, continuous treatment is suggested over fixed-duration treatment, unless fixed-duration treatment is preferred through shared decision-making.
- I, A
In most patients with relapsed or refractory CLL, fixed-duration venetoclax + anti-CD20 antibody or continuous treatment with a second-generation covalent BTK inhibitor are the preferred treatments.
- II, B (BTK-refractory); II/III, A (double-refractory)
Patients progressing on a covalent BTK inhibitor should be switched to venetoclax-based regimens or treated with a non-covalent BTK inhibitor. In "double-refractory" CLL (refractory to venetoclax and progressing on a covalent BTK inhibitor), pirtobrutinib (or, if unavailable, idelalisib + rituximab) is recommended and, in suitable patients, should be considered as a bridge to allogeneic transplantation.
- III, B
Vaccination against pneumococcus, varicella zoster virus and hepatitis B, and repeated seasonal vaccination against influenza and COVID-19, in all patients under monitoring; live vaccines should be avoided.
Study population
Patients with chronic lymphocytic leukaemia (CLL), small lymphocytic lymphoma (SLL) and Richter transformation; from diagnosis and active monitoring to first-line treatment, treatment of relapsed or refractory disease and management of Richter transformation.
Clinical significance and place in guidelines
The first CLL guideline developed independently by EHA with patient participation, intended to be updated every year. This guideline replaces the ESMO 2021 guideline for CLL and incorporates evidence from trials such as CLL14, ALPINE and A041202 into the treatment algorithm.
Limitations
Most recommendations are aligned with EMA approvals. Some recommendations (such as treatment after fixed-duration venetoclax) rest on lower-level evidence.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.