The first 60 days: Relapsed or refractory chronic lymphocytic leukaemia
When chronic lymphocytic leukaemia returns, the usual move is to switch drug class: venetoclax-based therapy after a BTK inhibitor, or a BTK inhibitor after venetoclax. Pirtobrutinib (BRUIN) works after the older BTK inhibitors fail, and CAR-T is approved for patients who have run out of both classes. Below, week by week, is what OnCo's record of Relapsed or refractory 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.
- Medical oncologistNamed in the standard of care for: Relapse after a BTK inhibitor, Relapse after venetoclax, Double-refractory after BTK inhibitor and venetoclax.
- Transplant and cell therapy teamNamed in the standard of care for: Double-refractory after BTK inhibitor and venetoclax.
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.Relapse after a BTK inhibitorNCCN Guidelines: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Venetoclax plus rituximab for two years (MURANO) or venetoclax-obinutuzumab; pirtobrutinib after covalent BTK inhibitor failure (BRUIN CLL-321).
Acalabrutinib or zanubrutinib (ALPINE) continuously, or ibrutinib; venetoclax retreatment if the prior remission lasted a year or more.
- 3.Double-refractory after BTK inhibitor and venetoclaxNCCN Guidelines: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Pirtobrutinib; lisocabtagene maraleucel CAR-T (TRANSCEND CLL 004); idelalisib-rituximab; clinical trials of BTK degraders, sonrotoclax and bispecifics; allogeneic transplant in fit young patients.
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 BTK C481S and PLCG2 resistance mutations, BCL2 G101V mutation, deland TP53 mutation re-tested at relapse, Complex karyotype, IGHV status), 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 Relapse after chemoimmunotherapy, Relapse after fixed-duration venetoclax, Progression on a covalent BTK inhibitor.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Relapse after a BTK inhibitor
- For my situation (relapse after a btk inhibitor), which of the standard options do you recommend and why?Guideline options include: Venetoclax plus rituximab for two years (MURANO) or venetoclax-obinutuzumab; pirtobrutinib after covalent BTK inhibitor failure (BRUIN CLL-321).
- Am I a candidate for Venetoclax, Rituximab, Obinutuzumab 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 BRUIN CLL-321 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Relapse after venetoclax
- For my situation (relapse after venetoclax), which of the standard options do you recommend and why?Guideline options include: Acalabrutinib or zanubrutinib (ALPINE) continuously, or ibrutinib; venetoclax retreatment if the prior remission lasted a year or more.
- Am I a candidate for Acalabrutinib, Zanubrutinib, 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 ALPINE and RESONATE apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Double-refractory after BTK inhibitor and venetoclax
- For my situation (double-refractory after btk inhibitor and venetoclax), which of the standard options do you recommend and why?Guideline options include: Pirtobrutinib; lisocabtagene maraleucel CAR-T (TRANSCEND CLL 004); idelalisib-rituximab; clinical trials of BTK degraders, sonrotoclax and bispecifics; allogeneic transplant in fit young patients.
- Am I a candidate for Pirtobrutinib, Lisocabtagene maraleucel, Idelalisib 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 TRANSCEND CLL 004 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Any stage
- Are there clinical trials I could join, for example of Pirtobrutinib, Sonrotoclax, Nemtabrutinib, Lisocabtagene maraleucel?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 after BTK inhibitor and venetoclax has no durable option”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Whether venetoclax retreatment works as well the second time, and after how long an interval”. 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.
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Relapsed or refractory chronic lymphocytic leukaemia: the full pageWhen chronic lymphocytic leukaemia returns, the usual move is to switch drug class: venetoclax-based therapy after a BTK inhibitor, or a BTK inhibitor after venetoclax. Pirtobrutinib (BRUIN) works after the older BTK inhibitors fail, and CAR-T is approved for patients who have run out of both classes.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- Drug resistance (primary and acquired): Why cancer drugs stop working: the tumour either never depended on the target or evolves around the block.
- Richter transformation: When slow CLL suddenly turns into an aggressive lymphoma.
- 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).
Every term links to the glossary.