The first 60 days: Chronic lymphocytic leukaemia, first treatment

Below, week by week, is what OnCo's record of Chronic lymphocytic leukaemia, first treatment says about the first two months: the order is typical, the timing is yours to ask about. Chronic lymphocytic leukaemia is treated only when it causes problems, and chemotherapy has gone. The first treatment is now either a BTK inhibitor taken indefinitely or a one-year course of venetoclax with obinutuzumab (CLL14), and the two can be combined for a fixed course. Sections appear only where the record has something to say. Orientation, not medical advice.

Weeks 1 to 2

What happens now

Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.

Biomarkers your report may list

del(17p) by FISH and TP53 mutation IGHV mutational status CLL-IPI score Beta-2 microglobulin Complex karyotype Undetectable MRD at end of fixed-duration therapy Cardiac risk factors before BTK inhibitors

Ask which of these were tested and what the results were; see the report reader for what each value means.

Tests and imaging linked to this cancer

Cytogenetics and FISH Multiparameter flow cytometry MRD

Weeks 1 to 3

Who is on your team

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.

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.

Weeks 2 to 6

Decisions coming up

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.Asymptomatic early-stage disease NCCN Guidelines: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Watch and wait with counts every three to twelve months; treat only on iwCLL indications.
Flow cytometry (immunophenotyping)IGHV mutational status del(17p) / TP53 aberration in CLL Cytogenetics and FISH
2.First treatment, fixed duration NCCN Guidelines: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Venetoclax plus obinutuzumab for 12 months (CLL14, CLL13); ibrutinib-venetoclax (GLOW, CAPTIVATE) or acalabrutinib-venetoclax with or without obinutuzumab (AMPLIFY) for fit patients.
Venetoclax Obinutuzumab CLL14 CLL13 / GAIA Ibrutinib Acalabrutinib GLOW CAPTIVATE AMPLIFY Venetoclax + obinutuzumab (12 months)BTK inhibitor + venetoclax, fixed duration
3.First treatment, continuous NCCN Guidelines: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Acalabrutinib (ELEVATE-TN) or zanubrutinib (SEQUOIA) until progression, preferred for del(17p) or TP53-mutated disease; ibrutinib where the newer agents are unavailable.
Acalabrutinib Zanubrutinib Ibrutinib ELEVATE-TN SEQUOIA Caution: ibrutinib in patients with cardiac risk
4.Chemoimmunotherapy NCCN Guidelines: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab only for IGHV-mutated disease without TP53 aberration where targeted drugs are unavailable; never for del(17p).
Fludarabine Cyclophosphamide Rituximab Bendamustine Chlorambucil Caution: chemoimmunotherapy in del(17p)/TP53 CLL

Every visit

Questions to ask at each visit

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 delby FISH and TP53 mutation, IGHV mutational status, CLL-IPI score, Beta-2 microglobulin, Complex karyotype), 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 Treatment-naive CLL without delor TP53 mutation, IGHV mutated, Treatment-naive CLL, IGHV unmutated, Treatment-naive CLL with delor TP53 mutation.
Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.

Asymptomatic early-stage disease

For my situation (asymptomatic early-stage disease), which of the standard options do you recommend and why?Guideline options include: Watch and wait with counts every three to twelve months; treat only on iwCLL indications.

First treatment, fixed duration

For my situation (first treatment, fixed duration), which of the standard options do you recommend and why?Guideline options include: Venetoclax plus obinutuzumab for 12 months (CLL14, CLL13); ibrutinib-venetoclax (GLOW, CAPTIVATE) or acalabrutinib-venetoclax with or without obinutuzumab (AMPLIFY) for fit patients.
Am I a candidate for Venetoclax, Obinutuzumab, Ibrutinib or related drugs, 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 treatment, continuous

For my situation (first treatment, continuous), which of the standard options do you recommend and why?Guideline options include: Acalabrutinib (ELEVATE-TN) or zanubrutinib (SEQUOIA) until progression, preferred for del(17p) or TP53-mutated disease; ibrutinib where the newer agents are unavailable.
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.

Chemoimmunotherapy

For my situation (chemoimmunotherapy), which of the standard options do you recommend and why?Guideline options include: Fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab only for IGHV-mutated disease without TP53 aberration where targeted drugs are unavailable; never for del(17p).
Am I a candidate for Fludarabine, Cyclophosphamide, Rituximab or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.

Any stage

Are there clinical trials I could join, for example of Sonrotoclax, Nemtabrutinib, CELESTIAL-TNCLL, CaDAnCe-304?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 “Continuous BTK inhibitor or fixed-duration venetoclax first: no head-to-head survival data”. How does that affect my plan?Open problems are where trials and second opinions matter most.
I read that “Whether MRD should decide how long fixed-duration therapy lasts”. How does that affect my plan?Open problems are where trials and second opinions matter most.

Weeks 3 to 8

Trials to ask about

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.

From day one

Help that costs nothing

Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.

Any time

What to read next

Words this page and the cancer page use

CLL-IPI (chronic lymphocytic leukaemia prognostic index): CLL-IPI scores five things at diagnosis (TP53 loss or mutation, unmutated IGHV, raised beta-2 microglobulin, advanced stage and age over 65) to predict time to first treatment and survival; TP53 and IGHV are the two that still change which drug is chosen, because they decide whether chemo-immunotherapy is ever an option.
IGHV mutational status: Whether the leukaemia's antibody gene has been 'edited' by the immune system.
del(17p) / TP53 aberration in CLL: A del(17p) deletion or TP53 mutation means loss or damage of the p53 safety gene in CLL.
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).
Flow cytometry (immunophenotyping): A machine that streams cells one by one past lasers and reads the surface proteins (CD markers) each carries, identifying what kind of cell it is.
TP53-mutated (p53-abnormal): Loss of the p53 'guardian of the genome', the most commonly mutated gene in cancer.
Tumour lysis syndrome (TLS): When a treatment kills cancer cells faster than the body can clear their contents, flooding the blood with potassium, phosphate and uric acid and injuring the kidneys and heart.

Every term links to the glossary.