The first 60 days: Chronic lymphocytic leukaemia
A slow leukaemia that no longer needs chemotherapy: BTK inhibitors and venetoclax control it for years, often in fixed-duration courses. Below, week by week, is what OnCo's record of Chronic lymphocytic leukaemia says about the first two months: the order is typical, the timing is yours to ask about. Sections appear only where the record has something to say. Orientation, not medical advice.
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
Ask which of these were tested and what the results were; see the report reader for what each value means.
These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.
- PathologistNamed in the standard of care for: Richter transformation.
- Medical oncologistNamed in the standard of care for: Frontline, Early stage, asymptomatic (Rai 0-II, Binet A-B), First-line, TP53-intact, fit or unfit, fixed duration, First-line, continuous BTK inhibition and 6 more.
- Transplant and cell therapy teamNamed in the standard of care for: Relapsed, First-line, del(17p) or TP53 mutation, Double-refractory (BTKi and BCL2i), Richter transformation.
- Palliative and supportive care teamNamed in the standard of care for: Supportive care throughout.
A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.
Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.
- 1.Early stage, asymptomatic (Rai 0-II, Binet A-B)NCCN category Category 1 (observation), NCCN CLL/SLL v2.2026
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.
BTK inhibitor continuous or venetoclax-based fixed duration.
- 3.First-line, TP53-intact, fit or unfit, fixed durationNCCN category Category 1 (venetoclax-obinutuzumab); Category 1 (acalabrutinib-venetoclax), ESMO-MCBS 4 (CLL14), NCCN CLL/SLL v2.2026
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.
- 4.First-line, continuous BTK inhibitionNCCN category Category 1 (acalabrutinib, zanubrutinib preferred), NCCN CLL/SLL v2.2026
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.
- 6.First-line, chemoimmunotherapy (limited role)NCCN category Category 2A (select patients), NCCN CLL/SLL v2.2026
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.
- 7.Progression on a covalent BTK inhibitorNCCN category Category 1 (venetoclax-rituximab); Category 2A (pirtobrutinib), NCCN CLL/SLL v2.2026
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.
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.
Alternate class; pirtobrutinib; CAR-T.
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.
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.
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.
Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?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?These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?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?Inherited variants can change treatment and matter for relatives.
Frontline
- For my situation (frontline), which of the standard options do you recommend and 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?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?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?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?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?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?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?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?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?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?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?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?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of SEQUOIA apply to someone like me?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?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?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of CLL13 / GAIA apply to someone like me?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?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?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?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?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?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?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?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?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?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?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?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, DZD8586, Rocbrutinib, Bexobrutideg?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?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?Supportive care improves quality of life and helps patients complete treatment.
- I read that “Double-refractory disease”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Richter transformation”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Trials open now for this cancer in OnCo, largest phase first. Joining a trial is a decision like any other: ask what the comparison arm is, whether a placebo is used, and what happens if you leave. The cancer page searches ClinicalTrials.gov live for more.
- A Study of Acalabrutinib Plus Venetoclax Versus Venetoclax Plus Obinutuzumab in Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic LymphomaPhase 3 · active · NCT05057494A Phase III Prospective, Multicenter, Randomized, Open-Label Trial of Acalabrutinib Plus Venetoclax Versus Venetoclax Plus Obinutuzumab in Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
- A Study of Acalabrutinib vs Investigator's Choice of Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in R/R CLLPhase 3 · active · NCT02970318A Randomized, Multicenter, Open-Label, Phase 3 Study of Acalabrutinib (ACP-196) Versus Investigator's Choice of Either Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Subjects With R/R Chronic Lymphocytic Leukemia
- 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) InhibitorsPhase 3 · active · NCT06970743A Phase 3, Open-Label, Randomized Study of BGB-16673 Compared to Investigator's Choice in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Previously Exposed to Covalent BTK Inhibitors
- A Study of DZD8586 Versus Investigator's Choice in r/r CLL/SLL (TAI-SHAN6)Phase 3 · recruiting · NCT07139873A Phase 3, Open-Label, Randomized, Multicenter Study to Evaluate Anti-tumor Efficacy of DZD8586 Versus Investigator's Choice in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
- 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).Phase 3 · recruiting · NCT05947851A Phase 3, Open-label, Randomized Study to Compare the Efficacy and Safety of Nemtabrutinib (MK-1026) Plus Venetoclax Versus Venetoclax Plus Rituximab in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Following at Least 1 Prior Therapy (BELLWAVE-010)
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Chronic lymphocytic leukaemia: the full pageA slow leukaemia that no longer needs chemotherapy: BTK inhibitors and venetoclax control it for years, often in fixed-duration courses.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Guidelines comparedNCCN, ESMO and NICE side by side for this cancer.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- del(17p) / TP53 aberration in CLL: A del(17p) deletion or TP53 mutation means loss or damage of the p53 safety gene in CLL.
- R-CHOP (lymphoma chemoimmunotherapy): R-CHOP is the standard first treatment for diffuse large B-cell lymphoma: rituximab (an antibody against CD20) plus four chemotherapy drugs (cyclophosphamide, doxorubicin, vincristine, prednisone), given every three weeks for six cycles with curative intent.
- Richter transformation: When slow CLL suddenly turns into an aggressive lymphoma.
- IGHV mutational status: Whether the leukaemia's antibody gene has been 'edited' by the immune system.
- Fixed-duration vs continuous therapy: Whether a drug is taken for a set period (say 12 months) and then stopped even though it is still working, or continued indefinitely until it fails.
- MRD-negative complete remission: MRD-negative complete remission means not just no leukaemia visible under the microscope, but none detectable with tests a thousand times more sensitive.
- Lymphoma (tissue type): Cancer of lymphocytes, the white blood cells of the immune system, usually growing as masses in lymph nodes, spleen or other organs.
- B cell: The immune cells that make antibodies.
- Leukaemia (tissue type): Cancer of the blood-forming cells in the bone marrow, which flood the blood with immature or abnormal white cells and crowd out normal blood production.
- Undetectable MRD (uMRD / MRD-negative): The test for leftover cancer cells found none, down to the sensitivity of the assay (often one cell in 100,000 or a million).
Every term links to the glossary.