Chronic lymphocytic leukaemia
A slow leukaemia that no longer needs chemotherapy: BTK inhibitors and venetoclax control it for years, often in fixed-duration courses.
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.
State of the art today
- 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.
Show survival figures (2)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- 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.
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- 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.
Where the cases are
Site: Leukaemia (all types) (shared total; subtype split not reported). World: 487,294 new cases, 305,405 deaths.
| # | Country | New cases | Deaths | Incidence ASR |
|---|---|---|---|---|
| 1 | China | 81,946 | 50,074 | |
| 2 | United States of America | 63,144 | 23,460 | |
| 3 | India | 49,883 | 36,871 | |
| 4 | Germany | 15,108 | 9,378 | |
| 5 | Russian Federation | 14,495 | 8,224 | |
| 6 | Indonesia | 13,959 | 10,370 | |
| 7 | Japan | 13,572 | 10,066 | |
| 8 | France (metropolitan) | 13,525 | 7,387 | |
| 9 | Brazil | 11,859 | 8,790 | |
| 10 | Italy | 10,799 | 7,197 |
GLOBOCAN reports leukaemia as one site; CLL is roughly a quarter of leukaemia in Western countries and rare in East Asia.
BTK inhibitor continuous or venetoclax-based fixed duration.
Alternate class; pirtobrutinib; CAR-T.
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.
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.
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.
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.
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.
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-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.
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.
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.
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.
Subtypes & biomarkers
top- 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)
- 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
Target prevalence in this cancer
| Target / alteration | Prevalence | Measure | Source |
|---|---|---|---|
| BTK (Bruton tyrosine kinase) Target is wild-type; resistance mutations arise on treatment | 100% | pathway dependence (BCR signalling), not a mutation | |
| CD19 | >95% | Surface expression | Wikipedia |
| BCL-2 | >90% | BCL-2 overexpression | Wikipedia |
| CD20 | >90% | Dim surface expression | Wikipedia |
| ROR1 | >90% | Surface expression | Wikipedia |
How common each drug target or alteration is in this cancer. Population-level and approximate; see the target page for detail. Full matrix.
- 1975Rai staging system
Clinical staging by lymphocytosis, nodes, organomegaly, cytopenias; Binet system follows in 1981.
- 1999IGHV mutational status predicts outcome
Hamblin and Damle show unmutated IGHV means aggressive disease.
- 2000Döhner hierarchical FISH model
del(17p) and del(11q) adverse; del(13q) favourable.
- 2010FCR: first regimen to improve survival
CLL8 shows fludarabine-cyclophosphamide-rituximab beats FC on OS; rituximab approved in CLL.
- 2013Obinutuzumab approved; ibrutinib debuts
CLL11 (obinutuzumab-chlorambucil) and ibrutinib's first approval (MCL).
- 2014Ibrutinib approved
- 2014Ibrutinib approved in CLL; RESONATE
PFS HR 0.22 vs ofatumumab; the BTK era begins. Idelalisib approved the same year.
- 2016Venetoclax approved
- 2016Venetoclax approved (del(17p)); ibrutinib first line
First BCL-2 inhibitor; RESONATE-2 moves ibrutinib to untreated CLL.
- 2019Fixed-duration therapy: CLL14; acalabrutinib approved
Venetoclax-obinutuzumab for 12 months; ELEVATE-TN and ASCEND establish acalabrutinib.
- 2022Ibrutinib-venetoclax fixed duration (EU); CLL13 and GLOW
Venetoclax combinations beat chemoimmunotherapy in fit patients; ibrutinib-venetoclax approved in Europe.
- 2023Zanubrutinib approved in CLL; ALPINE; pirtobrutinib accelerated approval
First BTKi to beat ibrutinib head to head; first non-covalent BTKi in CLL (December).
- 2024First CAR-T in CLL; AMPLIFY presented
Liso-cel accelerated approval (March); AMPLIFY fixed-duration acalabrutinib-venetoclax at ASH.
- 2025Pirtobrutinib traditional approval; sonrotoclax approved in China
BRUIN CLL-321 confirms benefit after covalent BTKi (3 December); next-generation BCL-2 inhibitor reaches patients.
- 2026Acalabrutinib frontline label expanded
- 2026First US all-oral fixed-duration regimen; sonrotoclax US approval (MCL); BTK degrader phase 3
Acalabrutinib-venetoclax approved 19 February; sonrotoclax accelerated approval 13 May; CaDAnCe-304 and CELESTIAL-TNCLL enrolling.
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 remain the leading cause of death; vaccine responses are blunted and COVID-19 mortality was high.
- 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.
Trials
topRecruiting now (live from ClinicalTrials.gov)
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Landmark trials in OnCo
Expert centres
topCentres linked to this cancer in OnCo
- via CAR-T cell therapy
- via CAR-T cell therapy
- via this cancer
- The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research InstituteColumbus, OH, USNCI comprehensivevia this cancer, Ibrutinib, Acalabrutinib, RESONATE
- Northwell Health Cancer InstituteNew Hyde Park, NY, USvia this cancer, CAR-T cell therapy, IGHV mutational status
- American Society of HematologyWashington, DC, USvia this cancer, CAR-T cell therapy
- via this cancer, CAR-T cell therapy
- via this cancer, CAR-T cell therapy
- European Hematology AssociationThe Hague, NLvia this cancer, CAR-T cell therapy
- Hospital Clínic de Barcelona / IDIBAPSBarcelona, ESvia this cancer, CAR-T cell therapy
- HOVONRotterdam, NLvia this cancer, Venetoclax
- via CAR-T cell therapy, Glofitamab
- Juravinski Cancer Centre / Escarpment Cancer Research InstituteHamilton, ON, CAvia CAR-T cell therapy, Allogeneic stem cell transplantation
- LYSA – The Lymphoma Study AssociationPierre-Bénite (Lyon), FRvia CAR-T cell therapy, Glofitamab
- Rigshospitalet – Copenhagen University HospitalCopenhagen, DKvia this cancer, CAR-T cell therapy
- Walter and Eliza Hall Institute of Medical ResearchMelbourne, AUvia this cancer, Venetoclax
- via CAR-T cell therapy
- via CAR-T cell therapy
- Advanced Research Projects Agency for HealthWashington, DC, USvia CAR-T cell therapy
- All India Institute of Medical Sciences, New DelhiNew Delhi, INvia CAR-T cell therapy
- via CAR-T cell therapy
- Central Drugs Standard Control OrganizationNew Delhi, INvia CAR-T cell therapy
- Chan Zuckerberg BiohubSan Francisco, USvia CAR-T cell therapy
- Children's Hospital of PhiladelphiaPhiladelphia, PA, USvia CAR-T cell therapy
- Chinese PLA General HospitalBeijing, CNvia CAR-T cell therapy
- Christian Medical College, VelloreVellore, INvia CAR-T cell therapy
- via CAR-T cell therapy
- City of Hope Orange CountyIrvine, CA, USvia CAR-T cell therapy
- Cleveland Clinic Abu DhabiAbu Dhabi, AEvia CAR-T cell therapy
- Comprehensive Cancer Center Freiburg (CCCF)Freiburg im Breisgau, DEvia this cancer
- via CAR-T cell therapy
- Dan L Duncan Comprehensive Cancer Center, Baylor College of MedicineHouston, TX, USNCI comprehensivevia CAR-T cell therapy
- European Medicines AgencyAmsterdam, NLvia CAR-T cell therapy
- via Allogeneic stem cell transplantation
- via CAR-T cell therapy
- Geneva University Hospitals (HUG)Geneva, CHvia CAR-T cell therapy
- GIMEMARome, ITvia this cancer
- via CAR-T cell therapy
- Hadassah Medical CenterJerusalem, ILvia CAR-T cell therapy
- Henan Cancer HospitalZhengzhou, CNvia CAR-T cell therapy
- via CAR-T cell therapy
- Hospital Universitario 12 de OctubreMadrid, ESvia CAR-T cell therapy
- via CAR-T cell therapy
- Indiana University Melvin and Bren Simon Comprehensive Cancer CenterIndianapolis, IN, USNCI comprehensivevia Allogeneic stem cell transplantation
- via CAR-T cell therapy
- Institut Paoli-CalmettesMarseille, FRvia CAR-T cell therapy
- via CAR-T cell therapy
- IRCCS Ospedale San RaffaeleMilan, ITvia CAR-T cell therapy
- via CAR-T cell therapy
- via CAR-T cell therapy
- via Allogeneic stem cell transplantation
- via CAR-T cell therapy
- via CAR-T cell therapy
- Multinational Association of Supportive Care in CancerAurora, ON, CAvia Cardio-oncology
- National Cancer Centre SingaporeSingapore, SGvia CAR-T cell therapy
- via CAR-T cell therapy
- via CAR-T cell therapy
- Nationwide Children's HospitalColumbus, OH, USvia CAR-T cell therapy
- NCI Center for Cancer Research (intramural programme)Bethesda, MD, USvia CAR-T cell therapy
- Nordic Lymphoma GroupStockholm, SEvia this cancer
- Peking University Cancer HospitalBeijing, CNvia CAR-T cell therapy
- via CAR-T cell therapy
- Ruijin Hospital, Shanghai Jiao Tong UniversityShanghai, CNvia CAR-T cell therapy
- via CAR-T cell therapy
- Seoul St. Mary's HospitalSeoul, KRvia CAR-T cell therapy
- Sheba Medical CenterRamat Gan, ILvia CAR-T cell therapy
- via CAR-T cell therapy
- Siriraj Hospital, Mahidol UniversityBangkok, THvia CAR-T cell therapy
- Society for Immunotherapy of CancerMilwaukee, WI, USvia CAR-T cell therapy
- via CAR-T cell therapy
- Taipei Veterans General HospitalTaipei, TWvia CAR-T cell therapy
- Texas Children's Cancer and Hematology CenterHouston, TX, USvia CAR-T cell therapy
- via CAR-T cell therapy
- via CAR-T cell therapy
- via this cancer
- via CAR-T cell therapy
- via CAR-T cell therapy
- University Cancer Center Frankfurt (UCT)Frankfurt am Main, DEvia CAR-T cell therapy
- via CAR-T cell therapy
- via CAR-T cell therapy
- via CAR-T cell therapy
- via this cancer
- via CAR-T cell therapy
- University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer CenterBaltimore, MD, USNCI comprehensivevia Allogeneic stem cell transplantation
Questions to ask
topQuestions to ask your oncologist about Chronic lymphocytic leukaemia
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example del/TP53, IGHV mutation status, del, BTK/PLCG2 resistance mutations, MRD), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include IGHV-mutated, IGHV-unmutated, deland/or TP53-mutated.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Frontline
- For my situation (frontline), which of the standard options do you recommend and why?Why: Guideline options include: BTK inhibitor continuous or venetoclax-based fixed duration.
- Am I a candidate for Venetoclax, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Relapsed
- For my situation (relapsed), which of the standard options do you recommend and why?Why: Guideline options include: Alternate class; pirtobrutinib; CAR-T.
Early stage, asymptomatic (Rai 0-II, Binet A-B)
- For my situation (early stage, asymptomatic (rai 0-ii, binet a-b)), which of the standard options do you recommend and why?Why: Guideline options include: 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.
- Am I a candidate for Ibrutinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
First-line, TP53-intact, fit or unfit, fixed duration
- For my situation (first-line, tp53-intact, fit or unfit, fixed duration), which of the standard options do you recommend and why?Why: Guideline options include: 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.
- Am I a candidate for Venetoclax, Obinutuzumab, Acalabrutinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of CLL14 and CLL13 / GAIA apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
First-line, continuous BTK inhibition
- For my situation (first-line, continuous btk inhibition), which of the standard options do you recommend and why?Why: Guideline options include: 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.
- Am I a candidate for Acalabrutinib, Zanubrutinib, Ibrutinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of ELEVATE-TN and SEQUOIA apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
First-line, del(17p) or TP53 mutation
- For my situation (first-line, del(17p) or tp53 mutation), which of the standard options do you recommend and why?Why: Guideline options include: 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.
- Am I a candidate for Zanubrutinib, Acalabrutinib, Venetoclax, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of SEQUOIA apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
First-line, chemoimmunotherapy (limited role)
- For my situation (first-line, chemoimmunotherapy (limited role)), which of the standard options do you recommend and why?Why: Guideline options include: 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.
- Am I a candidate for Rituximab, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of CLL13 / GAIA apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Relapse after fixed-duration venetoclax
- For my situation (relapse after fixed-duration venetoclax), which of the standard options do you recommend and why?Why: Guideline options include: 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.
- Am I a candidate for Venetoclax, Zanubrutinib, Acalabrutinib or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Progression on a covalent BTK inhibitor
- For my situation (progression on a covalent btk inhibitor), which of the standard options do you recommend and why?Why: Guideline options include: 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.
- Am I a candidate for Venetoclax, Pirtobrutinib, BGB-16673, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of BRUIN CLL-321 and CaDAnCe-304 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Double-refractory (BTKi and BCL2i)
- For my situation (double-refractory (btki and bcl2i)), which of the standard options do you recommend and why?Why: Guideline options include: 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.
- Am I a candidate for Pirtobrutinib, Lisocabtagene maraleucel, Sonrotoclax, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of TRANSCEND CLL 004 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Richter transformation
- For my situation (richter transformation), which of the standard options do you recommend and why?Why: Guideline options include: 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.
- Am I a candidate for Pirtobrutinib, Zanubrutinib, Glofitamab, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Supportive care throughout
- For my situation (supportive care throughout), which of the standard options do you recommend and why?Why: Guideline options include: 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.
Any stage
- Are there clinical trials I could join, for example of Venetoclax, Sonrotoclax, BGB-16673, Nemtabrutinib?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Double-refractory disease”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Richter transformation”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
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Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
12targets
10drugs
17companies
12institutions
16pathways
4terms
8trials
14pairings
4ideas
5collections
1people
7bottlenecks
2key papers
5AMPLIFY 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.
MURANO made fixed-duration venetoclax the standard for relapsed CLL and showed that stopping therapy after a deep response is safe for most patients. It also established MRD at end of treatment as a practical guide to who is likely to stay in remission. Retreatment with venetoclax at relapse appears feasible.
This paper is the proof-of-concept for a living drug: a single infusion of a patient's own engineered T cells could eradicate leukaemia that had survived chemotherapy, transplant and antibody therapy. It defined cytokine release syndrome and its antidote, tocilizumab, and revealed antigen-loss relapse. It led directly to the first approved gene-modified cell therapy three years later.
Latest papers
topQuery for this cancer: (TITLE:"Chronic lymphocytic leukaemia" OR ABSTRACT:"Chronic lymphocytic leukaemia") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Chronic lymphocytic leukaemia, not a curated reading list.