The first 60 days: Richter transformation of chronic lymphocytic leukaemia
Richter transformation is the sudden change of slow chronic lymphocytic leukaemia into a fast-growing lymphoma, usually of the diffuse large B-cell type. It is treated with lymphoma chemotherapy followed by a donor transplant where possible, and newer drugs such as pirtobrutinib, venetoclax combinations and bispecific antibodies are being tested because standard chemotherapy rarely cures it. Below, week by week, is what OnCo's record of Richter transformation 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.
Excision biopsy of the PET-hottest node, histology with clonality studies, TP53 and MYC testing; restage CLL and check for cause such as BTK inhibitor progression.
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: Diagnosis.
- RadiologistNamed in the standard of care for: Diagnosis.
- SurgeonNamed in the standard of care for: Diagnosis.
- Medical oncologistNamed in the standard of care for: Diagnosis, Diffuse large B-cell type, first treatment, Consolidation in responders, Relapsed or chemotherapy-refractory.
- Transplant and cell therapy teamNamed in the standard of care for: Diffuse large B-cell type, first treatment, Consolidation in responders, Relapsed or chemotherapy-refractory.
- Palliative and supportive care teamNamed in the standard of care for: Relapsed or chemotherapy-refractory.
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.Diffuse large B-cell type, first treatmentNCCN Guidelines: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
R-CHOP or R-EPOCH chemoimmunotherapy, with venetoclax added in trials; pirtobrutinib or a bispecific antibody in patients unfit for chemotherapy or within trials.
- 2.Consolidation in respondersNCCN Guidelines: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Allogeneic stem cell transplant for fit patients with a donor; autologous transplant where chemosensitive and no donor.
- 3.Relapsed or chemotherapy-refractoryNCCN Guidelines: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Clinical trial: bispecific antibodies (epcoritamab, glofitamab), BTK inhibitor with checkpoint inhibitor, CD19 CAR-T, pirtobrutinib; palliative care.
PirtobrutinibAcalabrutinibCAR-T cell therapySafety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's SyndromeACP-196 (Acalabrutinib), a Novel Bruton Tyrosine Kinase (BTK) Inhibitor, for Treatment of Chronic Lymphocytic Leukemia, Richter's Syndrome or Prolymphocytic Leukemia
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 PET-CT maximum SUV of the hottest node, Lactate dehydrogenase, Clonal relationship by IGHV sequencing, TP53, NOTCH1, CDKN2A and MYC lesions, Ki-67 on biopsy), 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 Richter transformation, diffuse large B-cell type, clonally related, Richter transformation, diffuse large B-cell type, clonally unrelated, Hodgkin-type Richter transformation.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Diagnosis
- For my situation (diagnosis), which of the standard options do you recommend and why?Guideline options include: Excision biopsy of the PET-hottest node, histology with clonality studies, TP53 and MYC testing; restage CLL and check for cause such as BTK inhibitor progression.
Diffuse large B-cell type, first treatment
- For my situation (diffuse large b-cell type, first treatment), which of the standard options do you recommend and why?Guideline options include: R-CHOP or R-EPOCH chemoimmunotherapy, with venetoclax added in trials; pirtobrutinib or a bispecific antibody in patients unfit for chemotherapy or within trials.
- Am I a candidate for Rituximab, Cyclophosphamide, Prednisone 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 Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Consolidation in responders
- For my situation (consolidation in responders), which of the standard options do you recommend and why?Guideline options include: Allogeneic stem cell transplant for fit patients with a donor; autologous transplant where chemosensitive and no donor.
Relapsed or chemotherapy-refractory
- For my situation (relapsed or chemotherapy-refractory), which of the standard options do you recommend and why?Guideline options include: Clinical trial: bispecific antibodies (epcoritamab, glofitamab), BTK inhibitor with checkpoint inhibitor, CD19 CAR-T, pirtobrutinib; palliative care.
- Am I a candidate for Pirtobrutinib, 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 Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome and ACP-196 (Acalabrutinib), a Novel Bruton Tyrosine Kinase (BTK) Inhibitor, for Treatment of Chronic Lymphocytic Leukemia, Richter's Syndrome or Prolymphocytic Leukemia 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, Venetoclax, Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome, ACP-196 (Acalabrutinib), a Novel Bruton Tyrosine Kinase (BTK) Inhibitor, for Treatment of Chronic Lymphocytic Leukemia, Richter's Syndrome or Prolymphocytic Leukemia?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 “No regimen reliably produces durable remission in clonally related disease”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Richter transformation is excluded from most trials, so evidence comes from small cohorts”. 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.
- ACP-196 (Acalabrutinib), a Novel Bruton Tyrosine Kinase (BTK) Inhibitor, for Treatment of Chronic Lymphocytic Leukemia, Richter's Syndrome or Prolymphocytic LeukemiaPhase 1/2 · active · NCT02029443A Phase 1/2, Multicenter, Open-label, and Dose-escalation Study of ACP-196 in Subjects With Chronic Lymphocytic Leukemia, Richter's Syndrome or Prolymphocytic Leukemia
- Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's SyndromePhase 1/2 · active · NCT04623541A Phase 1b/2, Open-Label, Safety and Efficacy Study of Epcoritamab (GEN3013; DuoBody®-CD3xCD20) in Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Richter transformation of chronic lymphocytic leukaemia: the full pageRichter transformation is the sudden change of slow chronic lymphocytic leukaemia into a fast-growing lymphoma, usually of the diffuse large B-cell type. It is treated with lymphoma chemotherapy followed by a donor transplant where possible, and newer drugs such as pirtobrutinib, venetoclax combinations and bispecific antibodies are being tested because standard chemotherapy rarely cures it.
- 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.
- 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.
- del(17p) / TP53 aberration in CLL: A del(17p) deletion or TP53 mutation means loss or damage of the p53 safety gene in CLL.
- TP53-mutated (p53-abnormal): Loss of the p53 'guardian of the genome', the most commonly mutated gene in cancer.
Every term links to the glossary.