Living with itChronic lymphocytic leukaemia

Back to the Chronic lymphocytic leukaemia hub →38 questions · 6 red cards

The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask.

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Decisions you may face

7 with more than one option · full decision page →

One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.

Frontline Relapsed Early stage, asymptomatic (Rai 0-II, Binet A-B)First-line, TP53-intact, fit or unfit, fixed duration3 First-line, continuous BTK inhibition3 First-line, del(17p) or TP53 mutation3 First-line, chemoimmunotherapy (limited role)Relapse after fixed-duration venetoclax4 Progression on a covalent BTK inhibitor3 Double-refractory (BTKi and BCL2i)4 Richter transformation4 Supportive care throughout

Red cards

From the labels and guidelines behind the standard of care. Your team's thresholds win.

Emergency services now
Major bleeding
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.
Acalabrutinib BGB-16673 Ibrutinib Pirtobrutinib Zanubrutinib source
Emergency services now
Tumour lysis syndrome
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.
Sonrotoclax Venetoclax source
Emergency services now
Cytokine release syndrome
Fever of 38 C or higher is grade 1 CRS; fever with low blood pressure, fast heartbeat, breathlessness or low oxygen is grade 2 or higher. The labels carry a boxed warning and say to report fever immediately.
Lisocabtagene maraleucel source
Emergency services now
Cytokine release syndrome
Fever of 38 C or higher, chills, low blood pressure, fast heartbeat or breathlessness, especially after a step-up dose. Boxed warning on teclistamab, epcoritamab, glofitamab, tarlatamab and blinatumomab.
Glofitamab source
Check before combining
Food and drink: Ibrutinib
Avoid grapefruit and Seville oranges.
Ibrutinib source
Check before combining
Food and drink: Venetoclax
Take with a meal and water. Avoid grapefruit, Seville oranges and starfruit.
Venetoclax source

See all on the product pages:Acalabrutinib BGB-16673 Glofitamab Ibrutinib Lisocabtagene maraleucel Pirtobrutinib Sonrotoclax Venetoclax Zanubrutinib·Printable cards in the navigator

Questions to ask

Bring to your appointment

Questions to ask your oncologist about Chronic lymphocytic leukaemia

Generated from this cancer's standard of care, biomarkers, and pipeline · 38 questions

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.
How do the results of CLL12 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

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, DZD8586, Rocbrutinib, Bexobrutideg?
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.

Newly diagnosed? Read the first 60 days with Chronic lymphocytic leukaemia, then print the one-page appointment sheet with room for the answers.

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Cancers·Chronic lymphocytic leukaemia