# Chronic lymphocytic leukaemia

Source: https://onco.cc/cancers/cll/  
OnCo record `cll` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A slow leukaemia that no longer needs chemotherapy: BTK inhibitors and venetoclax control it for years, often in fixed-duration courses.

## Summary

Chronic lymphocytic leukaemia is a slow accumulation of mature B cells in blood, marrow, and lymph nodes, diagnosed at a median age of 70 and often found incidentally. Prognosis is set at diagnosis by IGHV mutational status, TP53 status (del(17p) or mutation), and karyotype, and by the CLL-IPI. Around a third of patients never need treatment; the rest are watched until symptoms, cytopenias, or bulky or rapidly progressive disease meet iwCLL criteria.

Treatment abandoned chemotherapy within a decade. Continuous BTK inhibitors (ibrutinib 2014, then the better-tolerated acalabrutinib and zanubrutinib) and the BCL-2 inhibitor venetoclax replaced FCR and BR after RESONATE, ELEVATE-TN, SEQUOIA, CLL13, and CLL14. Two strategies now compete in first line: indefinite BTK inhibition, or fixed-duration therapy for 12-15 months with venetoclax-obinutuzumab (CLL14) or a BTK inhibitor plus venetoclax (acalabrutinib-venetoclax, the first all-oral fixed-duration regimen approved in the US in February 2026). Undetectable MRD at the end of fixed-duration therapy predicts years of treatment-free remission. Patients with del(17p)/TP53 aberration receive continuous BTK inhibition or venetoclax-based therapy and are excluded from chemoimmunotherapy entirely.

Relapse is treated by switching class: venetoclax after BTK inhibitor failure, or a BTK inhibitor after venetoclax; pirtobrutinib (non-covalent) works after covalent BTK inhibitors and gained full approval in December 2025; CAR-T (liso-cel, 2024) and allogeneic transplant are reserved for double-refractory disease. Next come BTK degraders (BGB-16673, phase 3), the next-generation BCL-2 inhibitor sonrotoclax (approved for mantle cell lymphoma in May 2026; CLL phase 3 reading out), and MRD-guided treatment duration. The unsolved problems are Richter transformation, double-refractory disease, infections and second cancers on long-term therapy, and the cost of indefinite treatment.

## Fields

- Kind: Cancer
- Last checked: 2026-09-04
- Tags: heme
- Group: haematologic
- Burden: About 20,000 US cases a year and 100,000 worldwide, the most common adult leukaemia in Western countries; median age 70; median survival now exceeds 10 years for most, approaching that of the age-matched population for IGHV-mutated patients.
- Subtypes: IGHV-mutated (indolent; long remissions after fixed-duration therapy); IGHV-unmutated (more aggressive; targeted therapy erases much of the gap); del(17p) and/or TP53-mutated (5-10% at diagnosis, up to 40% at relapse; continuous targeted therapy); del(11q) (ATM; historically adverse, neutralised by BTK inhibitors); Trisomy 12 (NOTCH1-associated); del(13q) alone (favourable); Complex karyotype (≥3 abnormalities; adverse); Small lymphocytic lymphoma (same disease, nodal presentation); Monoclonal B-cell lymphocytosis (precursor; 1-2% per year progress); Richter transformation (DLBCL or Hodgkin-type; 2-10% of patients)
- Biomarkers: del(17p)/TP53; IGHV mutation status; del(11q); BTK/PLCG2 resistance mutations; MRD; IGHV mutational status (<2% deviation = unmutated); TP53 mutation and del(17p) by FISH; FISH panel: del(13q), del(11q), trisomy 12, del(17p); Complex karyotype; NOTCH1, SF3B1, BIRC3 mutations; β2-microglobulin and CLL-IPI score; MRD by flow or clonoSEQ at end of fixed-duration therapy; BTK C481S/T474I/L528W and PLCG2 mutations at BTKi progression; BCL2 G101V and other mutations at venetoclax progression; Hepatitis B serology before anti-CD20 therapy

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/cll/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/cll/#overview [3 subtypes, 7 state-of-the-art points]
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/cll/#what-it-is [13 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/cll/#finding-it [15 biomarkers, 7 prevalence rows]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/cll/#treating-it [12 settings, 3 regimens, 7 decisions with options]
- Evidence (own page): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/cll/evidence/ [69 trials, 6 key papers, 16 milestones]
- The science (own page): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/cll/science/ [41 targets, 7 pathways, 4 preclinical models]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/cll/where-you-are/ [16 centres]
- Living with it (own page): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/cll/living-with-it/ [38 questions, 6 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/cll/coming/ [35 medicines, 69 trials, 5 ideas, 10 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/cll/data/ [296 connected records]

## Standard of care

- Frontline: BTK inhibitor continuous or venetoclax-based fixed duration. ([Venetoclax](https://onco.cc/drugs/venetoclax/))
- Relapsed: Alternate class; pirtobrutinib; CAR-T. ([CAR-T cell therapy](https://onco.cc/technologies/car-t/))
- Early stage, asymptomatic (Rai 0-II, Binet A-B): Watch and wait with periodic counts and examination; early treatment with ibrutinib (CLL12) delayed progression but did not improve survival and is not recommended. Vaccinations and infection prevention. ([Ibrutinib](https://onco.cc/drugs/ibrutinib/), [IGHV mutational status](https://onco.cc/terms/ighv-status/), [CLL12](https://onco.cc/trials/cll12/))
- First-line, TP53-intact, fit or unfit, fixed duration: Venetoclax + obinutuzumab for 12 months (CLL14, CLL13), or acalabrutinib + venetoclax for 14 cycles (AMPLIFY; approved February 2026), or ibrutinib + venetoclax 15 months (EU; GLOW, CAPTIVATE). uMRD at end of treatment predicts durable remission; retreatment is effective. ([Venetoclax](https://onco.cc/drugs/venetoclax/), [Obinutuzumab](https://onco.cc/drugs/obinutuzumab/), [Acalabrutinib](https://onco.cc/drugs/acalabrutinib/), [CLL14](https://onco.cc/trials/cll14/), [CLL13 / GAIA](https://onco.cc/trials/cll13-gaia/), [AMPLIFY](https://onco.cc/trials/amplify/), [BTK inhibitor + venetoclax, fixed duration](https://onco.cc/pairings/btki-plus-venetoclax-fixed-duration/))
- First-line, continuous BTK inhibition: Acalabrutinib (± obinutuzumab, ELEVATE-TN) or zanubrutinib (SEQUOIA) until progression; ibrutinib where alternatives are unavailable. Preferred for del(17p)/TP53 and for patients who cannot manage venetoclax ramp-up or TLS monitoring. ([Acalabrutinib](https://onco.cc/drugs/acalabrutinib/), [Zanubrutinib](https://onco.cc/drugs/zanubrutinib/), [Ibrutinib](https://onco.cc/drugs/ibrutinib/), [ELEVATE-TN](https://onco.cc/trials/elevate-tn/), [SEQUOIA](https://onco.cc/trials/sequoia/))
- First-line, del(17p) or TP53 mutation: Continuous second-generation BTK inhibitor (zanubrutinib: 5-year PFS 72%; acalabrutinib) or venetoclax-obinutuzumab; never chemoimmunotherapy; consider clinical trial and early referral for transplant/CAR-T planning if young. ([Zanubrutinib](https://onco.cc/drugs/zanubrutinib/), [Acalabrutinib](https://onco.cc/drugs/acalabrutinib/), [Venetoclax](https://onco.cc/drugs/venetoclax/), [SEQUOIA](https://onco.cc/trials/sequoia/), [del(17p) / TP53 aberration in CLL](https://onco.cc/terms/del17p-tp53/), [Caution: chemoimmunotherapy in del(17p)/TP53 CLL](https://onco.cc/pairings/cit-in-del17p-caution/))
- First-line, chemoimmunotherapy (limited role): FCR only for young, fit, IGHV-mutated, TP53-intact patients who decline targeted therapy or lack access; BR in older patients likewise. Outperformed by targeted therapy in CLL13, ELEVATE-TN, SEQUOIA, AMPLIFY. ([Rituximab](https://onco.cc/drugs/rituximab/), [CLL13 / GAIA](https://onco.cc/trials/cll13-gaia/))
- Relapse after fixed-duration venetoclax: Retreat with venetoclax-based therapy if remission lasted >2-3 years, or switch to a BTK inhibitor (acalabrutinib, zanubrutinib); pirtobrutinib if prior covalent BTKi as well. ([Venetoclax](https://onco.cc/drugs/venetoclax/), [Zanubrutinib](https://onco.cc/drugs/zanubrutinib/), [Acalabrutinib](https://onco.cc/drugs/acalabrutinib/), [Pirtobrutinib](https://onco.cc/drugs/pirtobrutinib/))
- Progression on a covalent BTK inhibitor: Venetoclax-based therapy (venetoclax-rituximab 24 months, MURANO) or pirtobrutinib (BRUIN CLL-321; traditional approval December 2025); BTK degraders (BGB-16673 vs pirtobrutinib, CaDAnCe-304) in trials. ([Venetoclax](https://onco.cc/drugs/venetoclax/), [Pirtobrutinib](https://onco.cc/drugs/pirtobrutinib/), [BGB-16673](https://onco.cc/drugs/bgb-16673/), [BRUIN CLL-321](https://onco.cc/trials/bruin-cll-321/), [CaDAnCe-304](https://onco.cc/trials/cadance-304/))
- Double-refractory (BTKi and BCL2i): Pirtobrutinib if BTK-naive-to-noncovalent; lisocabtagene maraleucel CAR-T (TRANSCEND CLL 004; accelerated approval 2024); allogeneic transplant in fit patients; PI3K inhibitors (idelalisib, duvelisib) rarely; clinical trials of degraders, sonrotoclax, bispecifics. ([Pirtobrutinib](https://onco.cc/drugs/pirtobrutinib/), [Lisocabtagene maraleucel](https://onco.cc/drugs/lisocabtagene-maraleucel/), [TRANSCEND CLL 004](https://onco.cc/trials/transcend-cll-004/), [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [Sonrotoclax](https://onco.cc/drugs/sonrotoclax/))
- Richter transformation: Biopsy to confirm and assess clonal relationship; chemoimmunotherapy (R-CHOP) has poor results; checkpoint inhibitor + BTK inhibitor (zanubrutinib-tislelizumab, RT1), pirtobrutinib, venetoclax-based regimens, CD20×CD3 bispecifics (epcoritamab, glofitamab), CAR-T; allogeneic transplant for responders. ([Richter transformation](https://onco.cc/terms/richter-transformation/), [Pirtobrutinib](https://onco.cc/drugs/pirtobrutinib/), [Zanubrutinib](https://onco.cc/drugs/zanubrutinib/), [Glofitamab](https://onco.cc/drugs/glofitamab/), [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/))
- Supportive care throughout: Infection prophylaxis and vaccination (non-live; reduced vaccine responses), IVIG for recurrent infections with hypogammaglobulinaemia, HBV screening before anti-CD20, skin cancer surveillance (second cancers), cardio-oncology review before ibrutinib, TLS prophylaxis with venetoclax. ([Tumour lysis syndrome (TLS)](https://onco.cc/terms/tumor-lysis-syndrome/), [Cardio-oncology](https://onco.cc/technologies/cardio-oncology/), [Caution: ibrutinib in patients with cardiac risk](https://onco.cc/pairings/btki-ibrutinib-cardiac-caution/))

## State of the art

- Chemotherapy-free care with near-normal life expectancy for many.
- Chemotherapy is essentially obsolete in CLL; median survival for most patients now approaches that of the general population.
- Two first-line philosophies with phase 3 support: indefinite BTK inhibition (acalabrutinib, zanubrutinib) or fixed-duration venetoclax combinations (venetoclax-obinutuzumab; acalabrutinib-venetoclax approved February 2026).
- Head-to-head data rank the BTK inhibitors: zanubrutinib beat ibrutinib on PFS and safety (ALPINE); acalabrutinib matched it with less cardiotoxicity (ELEVATE-RR).
- Sequencing works: BTKi → venetoclax → pirtobrutinib gives years of additional control; pirtobrutinib fully approved December 2025.
- uMRD at end of fixed-duration therapy is the key prognostic readout and is being tested as a stopping rule.
- First CAR-T in CLL (liso-cel, 2024), BTK degraders in phase 3, and sonrotoclax approved (MCL 2026) with CLL phase 3 reading out.

## Open problems

- Double-refractory disease.
- Richter transformation.
- Richter transformation: median survival still under a year for clonally related cases; no approved therapy.
- Double-refractory disease after BTKi and venetoclax: pirtobrutinib gives ~1 year; CAR-T complete responses are only ~20%.
- Fixed duration versus continuous therapy has never been compared head to head for OS; MAJIC and CLL17 will inform.
- Infections are the main threat to people living with CLL; vaccine responses are blunted and COVID-19 mortality was high, so prophylaxis and immunoglobulin replacement matter.
- Second primary cancers, especially skin, on long-term therapy.
- Cost: indefinite BTK inhibition costs more than $150,000 per year; access is limited in most of the world and biosimilar rituximab-based chemoimmunotherapy persists where targeted drugs are unaffordable.
- T-cell dysfunction in CLL limits CAR-T and bispecific efficacy; how to restore it (BTKi pre-treatment, allogeneic products) is open.
- Optimal MRD assay, compartment (blood vs marrow), and threshold for stopping therapy are not standardised.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Chronic_lymphocytic_leukemia
- NCCN CLL/SLL Insights v2.2026: https://jnccn.org/view/journals/jnccn/24/3/article-p68.xml
- iwCLL guidelines (Blood 2018): https://ashpublications.org/blood/article/131/25/2745/36953

## Connected records

- cancers: [Acute lymphoblastic leukaemia](https://onco.cc/cancers/all-leukemia/), [Chronic lymphocytic leukaemia, first treatment](https://onco.cc/cancers/cll-treatment-naive/), [Chronic myeloid leukaemia (CML)](https://onco.cc/cancers/cml/), [Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms](https://onco.cc/cancers/cmml/), [Hairy cell leukaemia](https://onco.cc/cancers/hairy-cell-leukemia/), [Leukaemia (all types)](https://onco.cc/cancers/leukaemia/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Relapsed or refractory chronic lymphocytic leukaemia](https://onco.cc/cancers/cll-relapsed/), [Richter transformation of chronic lymphocytic leukaemia](https://onco.cc/cancers/richter-transformation-cll/), [Splenic B-cell lymphoma/leukaemia with prominent nucleoli (formerly B-cell prolymphocytic leukaemia and hairy cell leukaemia variant)](https://onco.cc/cancers/splenic-b-cell-lymphoma-leukaemia-prominent-nucleoli/), [T-cell large granular lymphocytic leukaemia](https://onco.cc/cancers/t-large-granular-lymphocytic-leukaemia/), [T-cell prolymphocytic leukaemia](https://onco.cc/cancers/t-cell-prolymphocytic-leukaemia/)
- technologies: [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [BCL-2 inhibitors](https://onco.cc/technologies/bcl2-inhibitors/), [BH3 profiling (functional apoptosis testing)](https://onco.cc/technologies/bh3-profiling/), [CAR-T cell therapy](https://onco.cc/technologies/car-t/), [Cardio-oncology](https://onco.cc/technologies/cardio-oncology/), [Cytogenetics and FISH](https://onco.cc/technologies/cytogenetics-fish/), [Ex vivo drug sensitivity screening in blood cancers (EXALT)](https://onco.cc/technologies/functional-precision-medicine-haematology/), [Flow cytometers](https://onco.cc/technologies/flow-cytometers/), [Monoclonal antibodies](https://onco.cc/technologies/monoclonal-antibody/), [Multiparameter flow cytometry MRD](https://onco.cc/technologies/flow-cytometry-mrd/), [NGS-based MRD (clonoSEQ and molecular MRD)](https://onco.cc/technologies/ngs-mrd-clonoseq/), [PROTACs & molecular glues (targeted protein degradation)](https://onco.cc/technologies/protac-degrader/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [Adenosine deaminase (ADA)](https://onco.cc/targets/ada/), [AXIN2](https://onco.cc/targets/axin2/), [BAX](https://onco.cc/targets/bax/), [BCL-2](https://onco.cc/targets/bcl2/), [BIM (BCL2L11)](https://onco.cc/targets/bim/), [BIRC3](https://onco.cc/targets/birc3/), [BTG1](https://onco.cc/targets/btg1/), [BTG2](https://onco.cc/targets/btg2/), [BTK (Bruton tyrosine kinase)](https://onco.cc/targets/btk/), [CCND2](https://onco.cc/targets/ccnd2/), [CD19](https://onco.cc/targets/cd19/), [CD20](https://onco.cc/targets/cd20/), [CD52](https://onco.cc/targets/cd52/), [CHD2](https://onco.cc/targets/chd2/), [CNOT3](https://onco.cc/targets/cnot3/), [DTX1](https://onco.cc/targets/dtx1/), [EGR2](https://onco.cc/targets/egr2/), [FUBP1](https://onco.cc/targets/fubp1/), [H4C9](https://onco.cc/targets/h4c9/), [LYN kinase](https://onco.cc/targets/lyn/), [MAPK1](https://onco.cc/targets/mapk1/), [MED12](https://onco.cc/targets/med12/), [MGA](https://onco.cc/targets/mga/), [MYD88](https://onco.cc/targets/myd88/), [NFKBIE](https://onco.cc/targets/nfkbie/), [NXF1](https://onco.cc/targets/nxf1/), [PI3K delta (PIK3CD)](https://onco.cc/targets/pik3cd/), [PIK3CG](https://onco.cc/targets/pik3cg/), [PLCG2](https://onco.cc/targets/plcg2/), [POT1](https://onco.cc/targets/pot1/), [RIPK1](https://onco.cc/targets/ripk1/), [ROR1](https://onco.cc/targets/ror1/), [SALL4](https://onco.cc/targets/sall4/), [SETDB1](https://onco.cc/targets/setdb1/), [Thioredoxin reductase 1](https://onco.cc/targets/txnrd1/), [TP53](https://onco.cc/targets/tp53/), [ZMYM3](https://onco.cc/targets/zmym3/)
- drugs: [Acalabrutinib](https://onco.cc/drugs/acalabrutinib/), [Alemtuzumab](https://onco.cc/drugs/alemtuzumab/), [Bendamustine](https://onco.cc/drugs/bendamustine/), [Bexobrutideg](https://onco.cc/drugs/bexobrutideg/), [BGB-16673](https://onco.cc/drugs/bgb-16673/), [Chlorambucil](https://onco.cc/drugs/chlorambucil/), [clonoSEQ](https://onco.cc/drugs/clonoseq/), [CTX112](https://onco.cc/drugs/ctx112/), [Duvelisib](https://onco.cc/drugs/duvelisib/), [DZD8586](https://onco.cc/drugs/dzd8586/), [Emavusertib](https://onco.cc/drugs/emavusertib/), [Fludarabine](https://onco.cc/drugs/fludarabine/), [Fostamatinib](https://onco.cc/drugs/fostamatinib/), [Glofitamab](https://onco.cc/drugs/glofitamab/), [Human normal immunoglobulin (IVIg)](https://onco.cc/drugs/human-normal-immunoglobulin/), [Ibrutinib](https://onco.cc/drugs/ibrutinib/), [ICP-248](https://onco.cc/drugs/icp-248/), [Idelalisib](https://onco.cc/drugs/idelalisib/), [Imatinib](https://onco.cc/drugs/imatinib/), [KRT-232](https://onco.cc/drugs/krt-232/), [Lisocabtagene maraleucel](https://onco.cc/drugs/lisocabtagene-maraleucel/), [Nemtabrutinib](https://onco.cc/drugs/nemtabrutinib/), [Obinutuzumab](https://onco.cc/drugs/obinutuzumab/), [Ofatumumab](https://onco.cc/drugs/ofatumumab/), [Orelabrutinib](https://onco.cc/drugs/orelabrutinib/), [Pirtobrutinib](https://onco.cc/drugs/pirtobrutinib/), [Prednisone](https://onco.cc/drugs/prednisone/), [Rasburicase](https://onco.cc/drugs/rasburicase/), [Rituximab](https://onco.cc/drugs/rituximab/), [Rocbrutinib](https://onco.cc/drugs/rocbrutinib/), [Sonrotoclax](https://onco.cc/drugs/sonrotoclax/), [Umbralisib](https://onco.cc/drugs/umbralisib/), [Uracil mustard](https://onco.cc/drugs/uracil-mustard/), [Venetoclax](https://onco.cc/drugs/venetoclax/), [Zanubrutinib](https://onco.cc/drugs/zanubrutinib/)
- companies: [AbbVie (incl. ImmunoGen, Capstan)](https://onco.cc/companies/abbvie/), [Adaptive Biotechnologies](https://onco.cc/companies/adaptive-biotechnologies/), [Ascentage Pharma](https://onco.cc/companies/ascentage-pharma/), [AstraZeneca](https://onco.cc/companies/astrazeneca/), [Beckman Coulter](https://onco.cc/companies/beckman-coulter/), [BeOne Medicines (formerly BeiGene)](https://onco.cc/companies/beone/), [Bristol Myers Squibb](https://onco.cc/companies/bms/), [Curis](https://onco.cc/companies/curis/), [Dizal Pharmaceutical](https://onco.cc/companies/dizal/), [Eli Lilly (incl. Loxo)](https://onco.cc/companies/eli-lilly/), [Emergent BioSolutions](https://onco.cc/companies/emergent-biosolutions/), [German CLL Study Group](https://onco.cc/companies/german-cll-study-group/), [GIMEMA](https://onco.cc/companies/gimema/), [HOVON](https://onco.cc/companies/hovon/), [Infinity Pharmaceuticals](https://onco.cc/companies/infinity-pharmaceuticals/), [Johnson & Johnson](https://onco.cc/companies/johnson-johnson/), [Kartos Therapeutics](https://onco.cc/companies/kartos-therapeutics/), [Lupeng Pharmaceuticals](https://onco.cc/companies/lupeng-pharmaceuticals/), [Merck & Co. (MSD)](https://onco.cc/companies/merck/), [Mundipharma](https://onco.cc/companies/mundipharma/), [Nordic Lymphoma Group](https://onco.cc/companies/nordic-lymphoma-group/), [Nurix Therapeutics](https://onco.cc/companies/nurix/), [Outcomes4Me](https://onco.cc/companies/outcomes4me/), [Roche / Genentech](https://onco.cc/companies/roche-genentech/), [SecuraBio](https://onco.cc/companies/securabio/), [TG Therapeutics](https://onco.cc/companies/tg-therapeutics/), [Vironexis Biotherapeutics](https://onco.cc/companies/vironexis-biotherapeutics/)
- pathways: [B-cell receptor / BTK signalling (to NF-κB)](https://onco.cc/pathways/bcr-signalling/), [Complement in cancer](https://onco.cc/pathways/complement-in-cancer/), [Intrinsic apoptosis (BCL-2 family)](https://onco.cc/pathways/apoptosis-bcl2/), [Notch signalling](https://onco.cc/pathways/notch/), [PI3K / AKT / mTOR](https://onco.cc/pathways/pi3k-akt-mtor/), [RNA splicing](https://onco.cc/pathways/rna-splicing/), [The p53 network (guardian of the genome)](https://onco.cc/pathways/p53-mdm2-axis/)
- terms: [Active surveillance and observation](https://onco.cc/terms/active-surveillance-term/), [B cell](https://onco.cc/terms/b-cell/), [BTK C481S, PLCG2 and BCL2 G101V resistance mutations](https://onco.cc/terms/btki-bcl2i-resistance-mutations/), [CLL-IPI (chronic lymphocytic leukaemia prognostic index)](https://onco.cc/terms/cll-ipi/), [Cytogenetics and karyotype](https://onco.cc/terms/cytogenetics/), [del(17p) / TP53 aberration in CLL](https://onco.cc/terms/del17p-tp53/), [Fixed-duration vs continuous therapy](https://onco.cc/terms/fixed-duration/), [Flow cytometry (immunophenotyping)](https://onco.cc/terms/flow-cytometry/), [IGHV mutational status](https://onco.cc/terms/ighv-status/), [Leukaemia (tissue type)](https://onco.cc/terms/leukaemia-type/), [Lymphoma (tissue type)](https://onco.cc/terms/lymphoma-type/), [MRD-negative complete remission](https://onco.cc/terms/mrd-negative-cr/), [R-CHOP (lymphoma chemoimmunotherapy)](https://onco.cc/terms/r-chop/), [Richter transformation](https://onco.cc/terms/richter-transformation/), [SF3B1 mutation](https://onco.cc/terms/sf3b1-mutation/), [TP53-mutated (p53-abnormal)](https://onco.cc/terms/tp53-mutated/), [Tumour lysis syndrome (TLS)](https://onco.cc/terms/tumor-lysis-syndrome/), [Undetectable MRD (uMRD / MRD-negative)](https://onco.cc/terms/umrd/)
- trials: [A First-in-Human Study of HLA-Partially to Fully Matched Allogenic Cryopreserved Deceased Donor Bone Marrow Transplantation for Patients With Hematologic Malignancies](https://onco.cc/trials/nct05589896/), [A Phase 1/2 Study of IDP-121 in Patients With Relapsed/Refractory Hematologic Malignancies](https://onco.cc/trials/nct05908409/), [A Study Evaluating the Efficacy and Safety of Pirtobrutinib in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma](https://onco.cc/trials/nct06588478/), [A Study of Acalabrutinib Plus Venetoclax Versus Venetoclax Plus Obinutuzumab in Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma](https://onco.cc/trials/nct05057494/), [A Study of Acalabrutinib vs Investigator's Choice of Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in R/R CLL](https://onco.cc/trials/nct02970318/), [A Study of ACP-196 (Acalabrutinib) in Subjects With Relapsed/Refractory CLL and Intolerant of Ibrutinib Therapy](https://onco.cc/trials/nct02717611/), [A Study of AZD0486 Monotherapy or in Combination With Other Anti-Cancer Agents for Mature B-Cell Malignancies](https://onco.cc/trials/nct06564038/), [A Study of BGB-16673 Compared to Investigator's Choice in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Previously Exposed to Covalent Bruton Tyrosine Kinase (BTK) Inhibitors](https://onco.cc/trials/nct06970743/), [A Study of DZD8586 Combination in CLL/SLL (TAI-SHAN10)](https://onco.cc/trials/nct07154264/), [A Study of DZD8586 Versus Investigator's Choice in r/r CLL/SLL (TAI-SHAN6)](https://onco.cc/trials/tai-shan6/), [A Study of Emavusertib + An Approved Bruton Tyrosine Kinase Inhibitor (BTKi) in Participants With Chronic Lymphocytic Leukemia (CLL) and Other B-cell Malignancies](https://onco.cc/trials/nct07271667/), [A Study of GNC-035 in Relapsed or Refractory Chronic Lymphocytic Leukemia and Other Hematological Malignancies](https://onco.cc/trials/nct05944978/), [A Study of Lacutoclax (LP-108) in Patients With Relapsed/Refractory CLL/SLL](https://onco.cc/trials/nct07609823/), [A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010).](https://onco.cc/trials/nct05947851/), [A Study of Nemtabrutinib vs Chemoimmunotherapy for Participants With Previously Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Without TP53 Aberrations (MK-1026-008, BELLWAVE-008)](https://onco.cc/trials/nct05624554/), [A Study of NX-5948 in Adults With CLL/SLL Previously Treated With a Bruton's Tyrosine Kinase Inhibitor and a B-cell Lymphoma-2 Inhibitor (DAYBreak CLL-201)](https://onco.cc/trials/nct07221500/), [A Study of Pirtobrutinib (LOXO-305) Versus Bendamustine Plus Rituximab (BR) in Untreated Patients With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)](https://onco.cc/trials/nct05023980/), [A Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)](https://onco.cc/trials/nct05254743/), [A Study of Tacabrutideg (BGB-16673) Compared to Investigator's Choice in Participants With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Previously Exposed to Both Bruton Tyrosine Kinase (BTK) and B-cell Leukemia/Lymphoma 2 Protein (BCL2) Inhibitors](https://onco.cc/trials/nct06846671/), [A Study of Venetoclax in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma](https://onco.cc/trials/nct02966756/), [A Study to Customize Ibrutinib Treatment Regimens for Participants With Previously Untreated Chronic Lymphocytic Leukemia](https://onco.cc/trials/nct05963074/), [A Study to Evaluate Efficacy, Safety, and PK of XEMBIFY®+Standard Medical Treatment (SMT) Compared to Placebo+SMT to Prevent Infections in Participants With HGG and Recurrent or Severe Infections Associated With B-cell Chronic Lymphocytic Leukemia, Multiple Myeloma, and Non-Hodgkin Lymphoma](https://onco.cc/trials/nct05645107/), [A Study to Evaluate the Effect of Venetoclax on Participants Receiving a Covalent Bruton's Tyrosine Kinase Inhibitor (cBTKi) for First-line Chronic Lymphocytic Leukemia (1L CLL) to Achieve Deep Durable Remissions to Allow Off-treatment Period](https://onco.cc/trials/nct06524375/), [A Study to Evaluate the Risk of Tumor Lysis Syndrome (TLS) in Adult Participants Receiving Oral Venetoclax in Combination With Intravenously Infused Obinutuzumab or Oral Acalabrutinib for Previously Untreated Chronic Lymphocytic Leukemia (CLL)](https://onco.cc/trials/nct06428019/), [A Study to Evaluate the Safety and Efficacy of Tacabrutideg (BGB-16673) Compared to Pirtobrutinib in Adults With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma](https://onco.cc/trials/nct06973187/), [A Study to Investigate Progression-Free Survival With Sonrotoclax Plus Obinutuzumab Or Sonrotoclax Plus Rituximab Compared With Venetoclax Plus Rituximab Treatment In Patients With Relapsed and/or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CELESTIAL-RRCLL)](https://onco.cc/trials/nct06943872/), [A Study to Investigate Sonrotoclax (BGB-11417) Plus Zanubrutinib (BGB-3111) Compared With Venetoclax Plus Acalabrutinib in Adults With Previously Untreated Chronic Lymphocytic Leukemia](https://onco.cc/trials/nct07277231/), [A Study to Investigate Sonrotoclax Combined With Zanubrutinib Versus Zanubrutinib Alone in Participants With Previously Untreated Chronic Lymphocytic Leukemia](https://onco.cc/trials/nct06637501/), [A Trial of Pirtobrutinib (LOXO-305) Plus Venetoclax and Rituximab (PVR) Versus Venetoclax and Rituximab (VR) in Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)](https://onco.cc/trials/nct04965493/), [Acalabrutinib, Umbralisib, and Ublituximab (AU2) In Relapsed and Untreated CLL](https://onco.cc/trials/nct04624633/), [ACP-196 (Acalabrutinib), a Novel Bruton Tyrosine Kinase (BTK) Inhibitor, for Treatment of Chronic Lymphocytic Leukemia, Richter's Syndrome or Prolymphocytic Leukemia](https://onco.cc/trials/nct02029443/), [ALPINE](https://onco.cc/trials/alpine/), [AMPLIFY](https://onco.cc/trials/amplify/), [BELLWAVE-011](https://onco.cc/trials/bellwave-011/), [BRUIN CLL-321](https://onco.cc/trials/bruin-cll-321/), [CaDAnCe-304](https://onco.cc/trials/cadance-304/), [CAPTIVATE](https://onco.cc/trials/captivate/), [CELESTIAL-TNCLL](https://onco.cc/trials/celestial-tncll/), [CLL12](https://onco.cc/trials/cll12/), [CLL13 / GAIA](https://onco.cc/trials/cll13-gaia/), [CLL14](https://onco.cc/trials/cll14/), [DZD8586 in Patients With Relapsed or Refractory CLL/SLL (TAI-SHAN8)](https://onco.cc/trials/nct06539182/), [Efficacy and Safety of Nemtabrutinib (MK-1026) in Participants With Hematologic Malignancies (MK-1026-003)](https://onco.cc/trials/nct04728893/), [ELEVATE-TN](https://onco.cc/trials/elevate-tn/), [Fludarabine, Cyclophosphamide, and Rituximab Versus Pentostatin, Cyclophosphamide, and Rituximab in Previously Untreated or Treated B-Cell Chronic Lymphocytic Leukemia Patients](https://onco.cc/trials/nct00254163/), [Gene Therapy for CD19-Positive Hematologic Malignancies (SENTRY-CD19)](https://onco.cc/trials/nct06533579/), [GLOW](https://onco.cc/trials/glow/), [ICP-248 in Combination With Orelabrutinib in Treatment-naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (APEX-03)](https://onco.cc/trials/apex-03/), [MURANO](https://onco.cc/trials/murano/), [Phase 2 Study of Disease Risk Mutation-Guided Finite Acalabrutinib+Venetoclax for Relapsed CLL Post-1L Finite cBTKi+BCL2i ± Obinutuzumab](https://onco.cc/trials/nct07024706/), [RESONATE](https://onco.cc/trials/resonate/), [RESONATE-2](https://onco.cc/trials/resonate-2/), [ROCKET-CLL Global Phase 3 Study: Rocbrutinib vs Pirtobrutinib in cBTKi-Pretreated R/R CLL/SLL](https://onco.cc/trials/nct07342478/), [Safety and Efficacy of ALLO-501A Anti-CD19 Allogeneic CAR T Cells in Adults With Relapsed/Refractory Large B Cell Lymphoma, Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (ALPHA2)](https://onco.cc/trials/nct04416984/), [Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome](https://onco.cc/trials/nct04623541/), [SEQUOIA](https://onco.cc/trials/sequoia/), [Study of Acalabrutinib (ACP-196) Versus Ibrutinib in Previously Treated Participants With High Risk Chronic Lymphocytic Leukemia (CLL)](https://onco.cc/trials/nct02477696/), [Study of Acalabrutinib Versus Chlorambucil Plus Rituximab in Adult Subjects With Previously Untreated Chronic Lymphocytic Leukemia](https://onco.cc/trials/nct04075292/), [Study of APG-2575 in Patients With Relapsed/Refractory CLL/SLL](https://onco.cc/trials/nct05147467/), [Study of APG2575 Single Agent and Combination Therapy in Patients With Relapsed/Refractory CLL/SLL](https://onco.cc/trials/nct04494503/), [Study of BGB-11417 in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma](https://onco.cc/trials/nct05479994/), [Study of Iopofosine I-131 (CLR 131) in Select B-Cell Malignancies (CLOVER-1) With Expansion in Waldenstrom](https://onco.cc/trials/nct02952508/), [Study of NX-5948 in Combination With Other Agents in Adults With B-cell Malignancies](https://onco.cc/trials/nct07520006/), [Study of NX-5948 Versus Pirtobrutinib in R/R CLL/SLL](https://onco.cc/trials/nct07516093/), [Study to Assess Change in Disease Activity and Adverse Events of Oral Venetoclax With Intravenous (IV) Obinutuzumab in Adult Participants With Recurring Chronic Lymphocytic Leukemia (CLL)](https://onco.cc/trials/nct04895436/), [Study to Assess the Efficacy and Safety of Ublituximab in Combination With Umbralisib and Venetoclax Compared to Ublituximab in Combination With Umbralisib in Subjects With CLL (ULTRA-V)](https://onco.cc/trials/nct03801525/), [Surovatamig as Consolidation Therapy in Participants With Chronic Lymphocytic Leukaemia or Small Lymphocytic Lymphoma With Unmutated Immunoglobulin He](https://onco.cc/trials/nct07509151/), [Testing the Effectiveness of the Anti-cancer Drug, Mirdametinib, in Treating Relapsed, Refractory Chronic Lymphocytic Leukemia](https://onco.cc/trials/nct07061951/), [TRANSCEND CLL 004](https://onco.cc/trials/transcend-cll-004/)
- journals: [Blood cancer discovery](https://onco.cc/journals/blood-cancer-discovery/), [Blood cancer journal](https://onco.cc/journals/blood-cancer-journal/), [Clinical lymphoma, myeloma & leukemia](https://onco.cc/journals/clinical-lymphoma-myeloma-and-leukemia/), [Current hematologic malignancy reports](https://onco.cc/journals/current-hematologic-malignancy-reports/), [Haematologica](https://onco.cc/journals/haematologica/), [Journal of hematology & oncology](https://onco.cc/journals/journal-of-hematology-and-oncology/), [Leukemia & lymphoma](https://onco.cc/journals/leukemia-and-lymphoma/), [Leukemia research](https://onco.cc/journals/leukemia-research/)
- ideas: [A watch-and-wait registry for blood precursor conditions found by chance](https://onco.cc/ideas/idea-prev-blood-precursor-watch-registry/), [BTK degraders to pre-empt resistance in frontline CLL](https://onco.cc/ideas/idea-btk-degrader-frontline/), [MRD-guided treatment duration in CLL](https://onco.cc/ideas/idea-mrd-guided-stop-cll/), [Reduce the dose once the cancer responds: response-adapted de-escalation trials](https://onco.cc/ideas/idea-tr1-response-adapted-dose-reduction/), [Shared splice-derived neoantigens as off-the-shelf vaccine targets](https://onco.cc/ideas/idea-splice-neoantigens/)
- pairings: [BTK inhibitor + venetoclax, fixed duration](https://onco.cc/pairings/btki-plus-venetoclax-fixed-duration/), [Caution: chemoimmunotherapy in del(17p)/TP53 CLL](https://onco.cc/pairings/cit-in-del17p-caution/), [Caution: ibrutinib in patients with cardiac risk](https://onco.cc/pairings/btki-ibrutinib-cardiac-caution/), [Venetoclax + obinutuzumab (12 months)](https://onco.cc/pairings/venetoclax-plus-obinutuzumab/)
- institutions: [Alfred Health / Monash University](https://onco.cc/institutions/alfred-health-monash/), [American Society of Hematology](https://onco.cc/institutions/ash/), [Barts Cancer Institute / Barts Health NHS Trust](https://onco.cc/institutions/barts-cancer-institute/), [Comprehensive Cancer Center Freiburg (CCCF)](https://onco.cc/institutions/ccc-freiburg/), [Comprehensive Cancer Center Vienna, Medical University of Vienna / AKH](https://onco.cc/institutions/ccc-vienna/), [European Hematology Association](https://onco.cc/institutions/eha/), [Hospital Clínic de Barcelona / IDIBAPS](https://onco.cc/institutions/hospital-clinic-barcelona/), [Northwell Health Cancer Institute](https://onco.cc/institutions/northwell-cancer-institute/), [Rigshospitalet, Copenhagen University Hospital](https://onco.cc/institutions/rigshospitalet/), [The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute](https://onco.cc/institutions/osu-james/), [UC San Diego Moores Cancer Center](https://onco.cc/institutions/ucsd-moores/), [Ulm University Hospital / Comprehensive Cancer Center Ulm](https://onco.cc/institutions/ulm-university-hospital/), [Uniklinik Köln (CIO)](https://onco.cc/institutions/uniklinik-koeln/), [University Hospital Southampton / Centre for Cancer Immunology](https://onco.cc/institutions/southampton-cancer/), [University of Cincinnati Cancer Center](https://onco.cc/institutions/cincinnati-cancer-center/), [Walter and Eliza Hall Institute of Medical Research](https://onco.cc/institutions/wehi/)
- people: [Anthony Letai](https://onco.cc/people/anthony-letai/), [Antonio Cuneo](https://onco.cc/people/antonio-cuneo/), [Barbara Eichhorst](https://onco.cc/people/barbara-eichhorst/), [Carl H. June](https://onco.cc/people/carl-june/), [Catherine J. Wu](https://onco.cc/people/catherine-wu/), [Chris Hillis](https://onco.cc/people/chris-hillis/), [Constantine S. Tam](https://onco.cc/people/constantine-tam/), [David L. Porter](https://onco.cc/people/david-porter/), [Hagop M. Kantarjian](https://onco.cc/people/hagop-kantarjian/), [Jan A. Burger](https://onco.cc/people/jan-burger/), [Jennifer A. Woyach](https://onco.cc/people/jennifer-woyach/), [Jennifer R. Brown](https://onco.cc/people/jennifer-brown/), [John C. Byrd](https://onco.cc/people/john-byrd/), [John F. Seymour](https://onco.cc/people/john-seymour/), [Katayoun Rezvani](https://onco.cc/people/katy-rezvani/), [Kirsten Fischer](https://onco.cc/people/kirsten-fischer/), [Michael Hallek](https://onco.cc/people/michael-hallek/), [Owen N. Witte](https://onco.cc/people/owen-witte/), [Peter Hillmen](https://onco.cc/people/peter-hillmen/), [Sascha Dietrich](https://onco.cc/people/sascha-dietrich/), [Stanley R. Riddell](https://onco.cc/people/stanley-riddell/), [William G. Wierda](https://onco.cc/people/william-wierda/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [Older and multimorbid patients are excluded and undertreated](https://onco.cc/bottlenecks/b-aging-comorbidity/)
- collections: [Leukemia & Lymphoma Society (LLS)](https://onco.cc/collections/leukemia-lymphoma-society/)
- key papers: [AMPLIFY: fixed-duration acalabrutinib plus venetoclax, with or without obinutuzumab, versus chemo-immunotherapy in fit CLL patients](https://onco.cc/key-papers/paper-amplify-acalabrutinib-venetoclax-nejm-2025/), [CLL12: ibrutinib in early-stage chronic lymphocytic leukaemia, a randomised placebo-controlled phase 3 trial](https://onco.cc/key-papers/paper-cll12-ibrutinib-early-stage-langerbeins-jco-2025/), [CLL14: one year of venetoclax plus obinutuzumab instead of chemo-immunotherapy in older, less fit CLL patients](https://onco.cc/key-papers/paper-cll14-venetoclax-obinutuzumab-nejm-2019/), [ELEVATE-TN: acalabrutinib, alone or with obinutuzumab, against chemo-immunotherapy in untreated CLL](https://onco.cc/key-papers/paper-elevate-tn-acalabrutinib-lancet-2020/), [Maude 2014: CD19 CAR-T cells produce complete remission in 27 of 30 children and adults with relapsed ALL](https://onco.cc/key-papers/paper-maude-ctl019-all-nejm-2014/), [MURANO: two years of venetoclax plus rituximab versus chemo-immunotherapy in relapsed CLL](https://onco.cc/key-papers/paper-murano-venetoclax-rituximab-nejm-2018/)
- biomarkers: [CD20 expression (CD20-positive)](https://onco.cc/biomarkers/cd20-expression/), [TP53 mutation and del(17p)](https://onco.cc/biomarkers/tp53-del17p/)

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JSON: https://onco.cc/api/v1/entities/cll.json