Loading
Chronic lymphocytic leukaemia is treated only when it causes problems, and chemotherapy has gone. The first treatment is now either a BTK inhibitor taken indefinitely or a one-year course of venetoclax with obinutuzumab (CLL14), and the two can be combined for a fixed course.
Diagnosis needs 5 x 10^9/L clonal B cells with the typical CD5, CD19, CD23 phenotype; treatment starts only for iwCLL indications (symptoms, progressive anaemia or thrombocytopenia, bulky or fast-growing disease), because early treatment, even with ibrutinib in CLL12, has not lengthened life. Before the first treatment, every patient has FISH and sequencing for del(17p) and TP53 mutation and testing of IGHV mutational status, since these decide the regimen: TP53-aberrant disease does not respond durably to chemotherapy, and unmutated IGHV disease relapses early after it.
Two families of drugs replaced chemoimmunotherapy between 2014 and 2023. Continuous BTK inhibitors, ibrutinib and then the better-tolerated acalabrutinib (ELEVATE-TN, versus chlorambucil-obinutuzumab: median progression-free survival not reached at six years against 27.8 months) and zanubrutinib (SEQUOIA, versus bendamustine-rituximab, hazard ratio 0.42), control the disease for years but must be taken indefinitely and carry atrial fibrillation, bleeding and hypertension risks. Fixed-duration venetoclax with obinutuzumab for 12 months (CLL14, versus chlorambucil-obinutuzumab in older unfit patients: six-year progression-free survival 53.1 percent versus 21.7 percent, hazard ratio 0.40) gives most patients undetectable MRD and years off treatment; CLL13/GAIA confirmed the same in fit patients, where venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib beat fludarabine-based chemoimmunotherapy (five-year progression-free survival 69.8 and 81.3 percent against 50.7 percent).
The third option is an all-oral fixed-duration doublet: ibrutinib-venetoclax (GLOW in older patients, hazard ratio 0.216 for progression; CAPTIVATE; and the UK FLAIR trial with MRD-guided duration) and acalabrutinib-venetoclax with or without obinutuzumab (AMPLIFY, 2025), which in 2026 joined the approved first-line options. Choice now turns on comorbidity, TP53 status (continuous BTK inhibitor favoured), patient preference for a finite course, drug interactions and cost; non-covalent BTK inhibitors, BTK degraders, sonrotoclax and MRD-guided stopping are in first-line trials.
Chronic lymphocytic leukaemia is the commonest adult leukaemia in Western countries, with a median age at diagnosis of about 70; a third of patients never need treatment, and the rest start it when the disease causes symptoms, cytopenias or bulky nodes.
Leukaemias, myeloma and MDS live in the marrow and blood; lymphomas grow in lymph nodes and spleen. The node stations are the disease map, not a route of spread, and staging counts them.
In lymphoma the node stations are the disease itself; staging (Ann Arbor / Lugano) counts how many regions and sides of the diaphragm are involved.
Same organ: High-grade B-cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma), Mediastinal grey zone lymphoma, Primary effusion lymphoma, Plasmablastic lymphoma, T-cell/histiocyte-rich large B-cell lymphoma, EBV-positive diffuse large B-cell lymphoma, Primary large B-cell lymphoma of the testis, Gastric MALT lymphoma, Ocular adnexal MALT lymphoma, Extranodal NK/T-cell lymphoma, Adult T-cell leukaemia/lymphoma, ALK-positive anaplastic large cell lymphoma, ALK-negative anaplastic large cell lymphoma, Breast implant-associated anaplastic large cell lymphoma, Primary cutaneous anaplastic large cell lymphoma, Lymphomatoid papulosis, Mycosis fungoides, Enteropathy-associated T-cell lymphoma, Monomorphic epitheliotropic intestinal T-cell lymphoma, Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), Splenic marginal zone lymphoma, Nodal marginal zone lymphoma, Primary cutaneous marginal zone lymphoma, Primary cutaneous follicle centre lymphoma, Sezary syndrome, Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma), Hepatosplenic T-cell lymphoma, Intravascular large B-cell lymphoma, Lymphomatoid granulomatosis, T-cell prolymphocytic leukaemia, Splenic B-cell lymphoma/leukaemia with prominent nucleoli (formerly B-cell prolymphocytic leukaemia and hairy cell leukaemia variant), T-cell large granular lymphocytic leukaemia, Mixed-phenotype acute leukaemia, Myeloid leukaemia of Down syndrome, Burkitt leukaemia, Marginal zone lymphoma, Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome), Primary mediastinal (thymic) large B-cell lymphoma, Leukaemia (all types), Acute myeloid leukaemia, Acute lymphoblastic leukaemia, Chronic lymphocytic leukaemia, Chronic myeloid leukaemia (CML), Diffuse large B-cell lymphoma, Follicular lymphoma, Hodgkin lymphoma, Mantle cell lymphoma, Multiple myeloma, Non-Hodgkin lymphoma (all types), Myelodysplastic syndromes / neoplasms (MDS), Myeloproliferative neoplasms (PV, ET, myelofibrosis), Polycythaemia vera (PV), Essential thrombocythaemia (ET), Waldenström macroglobulinaemia, Hairy cell leukaemia, Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma), Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Burkitt lymphoma, HIV-associated (AIDS-related) lymphomas, Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Systemic mastocytosis, Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms, Langerhans cell histiocytosis (LCH), Post-transplant lymphoproliferative disorder (PTLD), FLT3-mutated acute myeloid leukaemia, IDH1- and IDH2-mutated acute myeloid leukaemia, NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia, Secondary and therapy-related acute myeloid leukaemia, Acute promyelocytic leukaemia, Acute myeloid leukaemia in older or unfit patients, Smouldering multiple myeloma, Newly diagnosed multiple myeloma, transplant-eligible, Newly diagnosed multiple myeloma, transplant-ineligible, Relapsed or refractory multiple myeloma, Plasma cell leukaemia, Lower-risk myelodysplastic syndromes, Higher-risk myelodysplastic syndromes, Relapsed or refractory chronic lymphocytic leukaemia, Richter transformation of chronic lymphocytic leukaemia, Chronic myeloid leukaemia, chronic phase, Chronic myeloid leukaemia, accelerated and blast phase, Primary myelofibrosis, Standard-risk B-cell acute lymphoblastic leukaemia in children, High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL), Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL), Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL), Infant acute lymphoblastic leukaemia (KMT2A-rearranged, under one year), Relapsed and refractory acute lymphoblastic leukaemia in children, Acute myeloid leukaemia in children, Erdheim-Chester disease, Rosai-Dorfman-Destombes disease, Single-system Langerhans cell histiocytosis (bone, skin or one other organ), Multisystem Langerhans cell histiocytosis (with or without risk-organ involvement), Indolent and smouldering systemic mastocytosis, Advanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia), Early-stage classical Hodgkin lymphoma (stage I to II), Advanced-stage classical Hodgkin lymphoma (stage III to IV), Nodular lymphocyte-predominant Hodgkin lymphoma (nodular lymphocyte-predominant B-cell lymphoma), Relapsed and refractory classical Hodgkin lymphoma
Watch and wait with counts every three to twelve months; treat only on iwCLL indications.
Venetoclax plus obinutuzumab for 12 months (CLL14, CLL13); ibrutinib-venetoclax (GLOW, CAPTIVATE) or acalabrutinib-venetoclax with or without obinutuzumab (AMPLIFY) for fit patients.
Acalabrutinib (ELEVATE-TN) or zanubrutinib (SEQUOIA) until progression, preferred for del(17p) or TP53-mutated disease; ibrutinib where the newer agents are unavailable.
Fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab only for IGHV-mutated disease without TP53 aberration where targeted drugs are unavailable; never for del(17p).
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Watch and wait remains the standard of care for early-stage chronic lymphocytic leukaemia irrespective of risk factors, even with a targeted drug available.
AMPLIFY delivered the first all-oral, fixed-duration doublet for front-line CLL and supported its approval, giving fit patients a way to avoid both chemotherapy and years of continuous BTK inhibitor. It does not settle whether a doublet or triplet is best, or how AV compares with venetoclax-obinutuzumab. Patients with TP53 aberration were excluded and still need different strategies.
ELEVATE-TN put a more selective BTK inhibitor into first-line CLL and, with the head-to-head ELEVATE-RR trial, showed it is as effective as ibrutinib with fewer cardiac side effects. Continuous acalabrutinib became one of the two main front-line options alongside fixed-duration venetoclax combinations. The trade-off is indefinite therapy and cost versus a time-limited course.
CLL14 established the first chemotherapy-free, fixed-duration regimen for front-line CLL and made MRD-guided thinking mainstream in the disease. Patients get a year of treatment and then a treatment-free period rather than indefinite therapy. The choice today is between fixed-duration venetoclax combinations and continuous BTK inhibitors, with no proven survival difference.
Query for this cancer: (TITLE:"Chronic lymphocytic leukaemia, first treatment" OR ABSTRACT:"Chronic lymphocytic leukaemia, first treatment" OR TITLE:"Treatment-naive CLL" OR ABSTRACT:"Treatment-naive CLL" OR TITLE:"Front-line CLL" OR ABSTRACT:"Front-line CLL" OR TITLE:"Previously untreated CLL" OR ABSTRACT:"Previously untreated CLL" OR TITLE:"First-line CLL therapy" OR ABSTRACT:"First-line CLL therapy") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Chronic lymphocytic leukaemia, first treatment, not a curated reading list.
The targets of this cancer's medicines and the ones linked to it directly.
Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Blood in stool or urine, vomiting blood, a bleed that will not stop, or a severe headache; fatal bleeding events have occurred and the labels advise considering the risk around surgery and with blood thinners.
Nausea, vomiting, muscle cramps, palpitations, seizures, confusion or passing much less urine in the first days of a new dose; the label requires hydration, anti-hyperuricaemic drugs and blood tests around each ramp-up step.
Avoid grapefruit and Seville oranges.
Take with a meal and water. Avoid grapefruit, Seville oranges and starfruit.
Possible QT prolongation. Check ECG and electrolytes; review other QT-prolonging drugs.
See all on the product pages:AcalabrutinibBendamustineChlorambucilCyclophosphamideIbrutinibVenetoclaxZanubrutinib·Printable cards in the navigator
Newly diagnosed? Read the first 60 days with Chronic lymphocytic leukaemia, first treatment, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record.
Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked.