The first 60 days: Waldenström macroglobulinaemia
A slow lymphoma that makes an abnormal IgM antibody, causing thick blood, anaemia and nerve damage. Nearly all cases share one mutation (MYD88 L265P), and BTK inhibitors control it for years. Below, week by week, is what OnCo's record of Waldenström macroglobulinaemia 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: Asymptomatic.
- SurgeonNamed in the standard of care for: Asymptomatic.
- Medical oncologistNamed in the standard of care for: Symptomatic, first line, Relapsed.
- Transplant and cell therapy teamNamed in the standard of care for: Relapsed.
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.
Observation; treat on symptoms, cytopenias, hyperviscosity or neuropathy, not on IgM level alone.
- 2.Symptomatic, first lineNCCN category Category 1 (zanubrutinib, ibrutinib ± rituximab; BR), NCCN Guidelines: WM/LPL
Bendamustine-rituximab or dexamethasone-rituximab-cyclophosphamide for fixed duration; or zanubrutinib / ibrutinib (± rituximab) continuously; plasmapheresis first for hyperviscosity.
Switch class (BTKi ↔ chemo-immunotherapy); bortezomib- or carfilzomib-based regimens; venetoclax; pirtobrutinib after covalent BTKi; autologous transplant in selected 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 MYD88 L265P, CXCR4 mutation, Serum IgM and viscosity, IPSSWM / rIPSSWM, Anti-MAG antibodies), 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 MYD88-mutant, CXCR4-wild-type, MYD88-mutant, CXCR4-mutant, MYD88-wild-type.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Asymptomatic
- For my situation (asymptomatic), which of the standard options do you recommend and why?Guideline options include: Observation; treat on symptoms, cytopenias, hyperviscosity or neuropathy, not on IgM level alone.
Symptomatic, first line
- For my situation (symptomatic, first line), which of the standard options do you recommend and why?Guideline options include: Bendamustine-rituximab or dexamethasone-rituximab-cyclophosphamide for fixed duration; or zanubrutinib / ibrutinib (± rituximab) continuously; plasmapheresis first for hyperviscosity.
- Am I a candidate for Bendamustine, Rituximab, Zanubrutinib or related drugs, 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: Switch class (BTKi ↔ chemo-immunotherapy); bortezomib- or carfilzomib-based regimens; venetoclax; pirtobrutinib after covalent BTKi; autologous transplant in selected young patients.
- Am I a candidate for Bortezomib, Carfilzomib, Venetoclax 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 Pirtobrutinib, Venetoclax, Zanubrutinib?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 “Indefinite BTKi therapy: cost, toxicity and resistance (BTK C481S)”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “CXCR4-mutant disease responds slower and shallower”. 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 to Investigate Efficacy and Safety of BCL2 Inhibitor Sonrotoclax as Monotherapy and in Combination With Zanubrutinib in Adults With Waldenström MacroglobulinemiaPhase 2 · active · NCT05952037An Open-Label, Multicenter Phase 2 Study to Evaluate the Efficacy and Safety of the BCL2 Inhibitor Sonrotoclax (BGB-11417) as Monotherapy and in Combination With Zanubrutinib (BGB-3111) in Patients With Waldenström Macroglobulinemia
- An Open-label, Phase 2 Study of ACP-196 in Subjects With Waldenström MacroglobulinemiaPhase 2 · active · NCT02180724An Open-label, Phase 2 Study of ACP-196 in Subjects With Waldenström Macroglobulinemia
- Study of Iopofosine I-131 (CLR 131) in Select B-Cell Malignancies (CLOVER-1) With Expansion in WaldenstromPhase 2 · active · NCT02952508An Open-Label, Multicenter, Phase 2 Study of Iopofosine I 131 (CLR 131) in Patients With Relapsed or Refractory (R/R) Select B-Cell Malignancies (CLOVER-1) and Expansion Cohort in Patients With Waldenstrom Macroglobulinemia (CLOVER-WaM)
- Study to Assess Change in Disease Activity of Oral Venetoclax in Adult Participants With Recurring Relapsed or Refractory (R/R) Waldenström MacroglobuPhase 2 · active · NCT07387471A Phase 2 Study of Venetoclax Monotherapy in Japanese Subjects With Relapsed or Refractory Waldenström Macroglobulinemia/Lymphoplasmacytic Lymphoma
- Dose Escalation and Dose Expansion Study of MDX2003 in Patients With Different Types of LymphomaPhase 1/2 · recruiting · NCT07249905A Phase 1/2 Clinical Study Evaluating MDX2003 in Participants With Relapsed, Progressive, or Refractory B-Cell Malignancies
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Waldenström macroglobulinaemia: the full pageA slow lymphoma that makes an abnormal IgM antibody, causing thick blood, anaemia and nerve damage. Nearly all cases share one mutation (MYD88 L265P), and BTK inhibitors control it for years.
- 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.
- IGHV mutational status: Whether the leukaemia's antibody gene has been 'edited' by the immune system.
- Histologic transformation: When a lung adenocarcinoma escapes targeted therapy by turning into a different cell type, usually small-cell.
Every term links to the glossary.