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.
Overview
Suspected when a patient with CLL develops a rapidly enlarging node, fever, weight loss, a sharply rising lactate dehydrogenase or a new bright focus on PET-CT, and confirmed by excision biopsy of the hottest node. About 95 percent of cases are diffuse large B-cell lymphoma and the rest Hodgkin-type; the distinction that matters most is clonal relationship to the CLL, since the 80 percent of large-cell cases that share the CLL's immunoglobulin rearrangement carry TP53, NOTCH1, CDKN2A and MYC lesions and do badly, while clonally unrelated cases behave like ordinary de novo lymphoma. Transformation can occur on any therapy, including BTK inhibitors and venetoclax, and is sometimes the reason a CLL treatment seems to fail.
Standard treatment is anthracycline-based chemoimmunotherapy, R-CHOP or R-EPOCH, with responses in fewer than half of clonally related cases and remissions that are short unless consolidated by an allogeneic stem cell transplant, which offers long-term survival to a minority of fit patients who respond. Autologous transplant is an option in chemosensitive disease when no donor is available. Hodgkin-type transformation is treated with Hodgkin regimens and has a better outlook.
Every new CLL and lymphoma drug is being tried: venetoclax added to R-EPOCH, the non-covalent BTK inhibitor pirtobrutinib (active in the BRUIN Richter cohort), covalent BTK inhibitors with checkpoint inhibitors (nivolumab or pembrolizumab with ibrutinib or acalabrutinib), the CD20 x CD3 bispecific antibodies epcoritamab and glofitamab, and CD19 CAR-T in small series, with response rates that are encouraging but durations still measured in months. Richter transformation is excluded from most CLL and lymphoma trials, so dedicated studies remain small.
State of the art
- Pirtobrutinib, venetoclax combinations and CD20 bispecifics produce responses in a disease where chemotherapy usually fails.
- Clonal relationship to the CLL is the single most important prognostic fact.
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- Chemoimmunotherapy with allogeneic transplant consolidation is the only route to long-term survival, and reaches a minority.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowMajor 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.
- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Emergency services nowTumour 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.
- Check before combiningFood and drink: Venetoclax
Take with a meal and water. Avoid grapefruit, Seville oranges and starfruit.
- Check before combiningLiver: Acalabrutinib
Avoid in severe impairment.
- Check before combiningLiver: Venetoclax
Reduce by 50% in severe impairment.
See all on the product pages:AcalabrutinibCyclophosphamidePirtobrutinibVenetoclax·Printable cards in the navigator
Anatomy and lymph node drainage
- Bone marrow (leukaemia, MDS, MPN, myeloma)
- Lymph node germinal centre (lymphomas)
- Spleen
- Blood (leukaemic phase)
- Lytic bone lesions (myeloma)
- Skin and extranodal sites
- Nodes: cervical
- Nodes: axillary
- Nodes: mediastinal
- Nodes: para-aortic and mesenteric
- Nodes: inguinal
Leukaemias, myeloma and MDS live in the marrow and blood; lymphomas grow in lymph nodes and spleen. The node stations are the disease map, not a route of spread, and staging counts them.
- Bone marrow (leukaemia, MDS, MPN, myeloma)Richter transformation, diffuse large B-cell type, clonally related (TP53, NOTCH1, CDKN2A, MYC) · Richter transformation, diffuse large B-cell type, clonally unrelated · Hodgkin-type Richter transformation · Richter transformation on BTK inhibitor or venetoclax therapy
- Lymph node germinal centre (lymphomas)Hodgkin-type Richter transformation
- Spleen
- Blood (leukaemic phase)
- Lytic bone lesions (myeloma)
- Skin and extranodal sites
- cervical
- axillary
- mediastinal
- para-aortic and mesenteric
- inguinal
In lymphoma the node stations are the disease itself; staging (Ann Arbor / Lugano) counts how many regions and sides of the diaphragm are involved.
Same organ: Marginal zone lymphoma, Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome), Primary mediastinal (thymic) large B-cell lymphoma, Leukaemia (all types), Acute myeloid leukaemia, Acute lymphoblastic leukaemia, Chronic lymphocytic leukaemia, Chronic myeloid leukaemia (CML), Diffuse large B-cell lymphoma, Follicular lymphoma, Hodgkin lymphoma, Mantle cell lymphoma, Multiple myeloma, Non-Hodgkin lymphoma (all types), Myelodysplastic syndromes / neoplasms (MDS), Myeloproliferative neoplasms (PV, ET, myelofibrosis), Polycythaemia vera (PV), Essential thrombocythaemia (ET), Waldenström macroglobulinaemia, Hairy cell leukaemia, Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma), Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Burkitt lymphoma, HIV-associated (AIDS-related) lymphomas, Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Systemic mastocytosis, Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms, Langerhans cell histiocytosis (LCH), Post-transplant lymphoproliferative disorder (PTLD), FLT3-mutated acute myeloid leukaemia, IDH1- and IDH2-mutated acute myeloid leukaemia, NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia, Secondary and therapy-related acute myeloid leukaemia, Acute promyelocytic leukaemia, Acute myeloid leukaemia in older or unfit patients, Smouldering multiple myeloma, Newly diagnosed multiple myeloma, transplant-eligible, Newly diagnosed multiple myeloma, transplant-ineligible, Relapsed or refractory multiple myeloma, Plasma cell leukaemia, Lower-risk myelodysplastic syndromes, Higher-risk myelodysplastic syndromes, Chronic lymphocytic leukaemia, first treatment, Relapsed or refractory chronic lymphocytic leukaemia, Chronic myeloid leukaemia, chronic phase, Chronic myeloid leukaemia, accelerated and blast phase, Primary myelofibrosis
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- Between two and ten percent of people with chronic lymphocytic leukaemia develop Richter transformation, an aggressive lymphoma arising from the leukaemia; when the lymphoma is clonally related to the CLL, median survival has historically been under a year.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
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.
R-CHOP or R-EPOCH chemoimmunotherapy, with venetoclax added in trials; pirtobrutinib or a bispecific antibody in patients unfit for chemotherapy or within trials.
Allogeneic stem cell transplant for fit patients with a donor; autologous transplant where chemosensitive and no donor.
Clinical trial: bispecific antibodies (epcoritamab, glofitamab), BTK inhibitor with checkpoint inhibitor, CD19 CAR-T, pirtobrutinib; palliative care.
Subtypes & biomarkers
top- Richter transformation, diffuse large B-cell type, clonally related (TP53, NOTCH1, CDKN2A, MYC)
- Richter transformation, diffuse large B-cell type, clonally unrelated
- Hodgkin-type Richter transformation
- Richter transformation on BTK inhibitor or venetoclax therapy
- 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
- Hodgkin versus large B-cell histology
- Circulating tumour DNA (research)
How often this target appears
- 1928Maurice Richter describes reticular cell sarcoma arising in chronic lymphocytic leukaemia
- 2011Rossi and colleagues show clonally related transformation carries TP53 and NOTCH1 lesions and a poor outcome
- 2013Richter transformation described on ibrutinib, a mode of BTK inhibitor failure
- 2023Pirtobrutinib and bispecific antibodies report activity in Richter cohorts
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 5 changes by month →- 2026-09-17This recordRichter transformation of chronic lymphocytic leukaemiaFacts on this page last checked
When this page itself was last checked or edited.
- 2023MilestonePirtobrutinibPirtobrutinib and bispecific antibodies report activity in Richter cohorts
A milestone in how this cancer is treated.
- 2013MilestoneIbrutinibRichter transformation described on ibrutinib, a mode of BTK inhibitor failure
A milestone in how this cancer is treated.
- 2011MilestoneTP53-mutated (p53-abnormal)Rossi and colleagues show clonally related transformation carries TP53 and NOTCH1 lesions and a poor outcome
A milestone in how this cancer is treated.
- 1928MilestoneRichter transformationMaurice Richter describes reticular cell sarcoma arising in chronic lymphocytic leukaemia
A milestone in how this cancer is treated.
What is in development for Richter transformation of chronic lymphocytic leukaemia, drawn from the whole corpus: 2 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Trials under way · 2
- Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome · phase 1/2 · Genmab
- ACP-196 (Acalabrutinib), a Novel Bruton Tyrosine Kinase (BTK) Inhibitor, for Treatment of Chronic Lymphocytic Leukemia, Richter's Syndrome or Prolymphocytic Leukemia · phase 1/2 · Acerta Pharma BV
Open problems and what is being done
No regimen reliably produces durable remission in clonally related disease.
Richter transformation is excluded from most trials, so evidence comes from small cohorts.
Predicting which CLL patients will transform, and whether BTK inhibitors change that risk.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Landmark trials
Expert centres
topExpert centres
New York · cancer center | United States | 0 | 5,100 | 94,456 | #1 | ||
Stanford · university | United States | 0 | 3,000 | 50,162 | #30 | ||
| China | none recorded | 0 | 4,959 | 62,355 | - | ||
Philadelphia · cancer center | United States | 0 | 3,148 | 54,267 | - | ||
Wuhan · hospital | China | none recorded | 0 | 2,478 | 31,527 | - | |
London · hospital | United Kingdom | none recorded | 0 | 2,376 | 28,940 | - | |
Seattle · cancer center | United States | 0 | 2,123 | 29,954 | - | ||
New Delhi · government | India | none recorded | 0 | 2,028 | 15,043 | - | |
Duarte, CA · cancer center | United States | 0 | 1,546 | 20,319 | - | ||
Houston, TX · cancer center | United States | 0 | 1,488 | 18,490 | - | ||
Beijing · cancer center | China | none recorded | 0 | 1,344 | 18,195 | - | |
Bethesda, MD · government | United States | none recorded | 0 | 1,312 | 26,262 | - | |
Vienna · cancer center | Austria | none recorded | 0 | 1,266 | 17,145 | - | |
Barcelona · hospital | Spain | none recorded | 0 | 1,265 | 15,631 | - | |
Wuhan · hospital | China | none recorded | 0 | 1,174 | 14,691 | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Richter transformation of chronic lymphocytic leukaemia but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Richter transformation of chronic lymphocytic leukaemia
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 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?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 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?Why: Inherited variants can change treatment and matter for relatives.
Diagnosis
- For my situation (diagnosis), which of the standard options do you recommend and why?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?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?Why: 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?Why: 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?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?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?Why: 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?Why: 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?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 “No regimen reliably produces durable remission in clonally related disease”. How does that affect my plan?Why: 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?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Richter transformation of chronic lymphocytic leukaemia, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
9targets
5drugs
7companies
9terms
4trials
2Latest papers
topQuery for this cancer: (TITLE:"Richter transformation of chronic lymphocytic leukaemia" OR ABSTRACT:"Richter transformation of chronic lymphocytic leukaemia" OR TITLE:"Richter syndrome" OR ABSTRACT:"Richter syndrome" OR TITLE:"Richter's transformation" OR ABSTRACT:"Richter's transformation" OR TITLE:"CLL transformed to diffuse large B-cell lymphoma" OR ABSTRACT:"CLL transformed to diffuse large B-cell lymphoma" OR TITLE:"Transformed CLL" OR ABSTRACT:"Transformed CLL") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Richter transformation of chronic lymphocytic leukaemia, not a curated reading list.
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