# Richter transformation of chronic lymphocytic leukaemia

Source: https://onco.cc/cancers/richter-transformation-cll/  
OnCo record `richter-transformation-cll` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: Richter syndrome; Richter's transformation; CLL transformed to diffuse large B-cell lymphoma; Transformed CLL
- Tags: subtype-page
- Group: haematologic
- Burden: 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.
- Subtypes: 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
- Biomarkers: 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)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/richter-transformation-cll/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/richter-transformation-cll/#overview [6 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/richter-transformation-cll/#what-it-is [4 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/richter-transformation-cll/#finding-it [7 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/richter-transformation-cll/#treating-it [4 settings, 3 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/richter-transformation-cll/#evidence [2 trials, 2 key papers, 4 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/richter-transformation-cll/#science [8 targets, 3 pathways]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/richter-transformation-cll/where-you-are/
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/richter-transformation-cll/#living-with-it [17 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/richter-transformation-cll/coming/ [7 medicines, 2 trials, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/richter-transformation-cll/data/ [55 connected records]

## Standard of care

- Diagnosis: 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. ([PET/CT](https://onco.cc/technologies/pet-ct/), [Richter transformation](https://onco.cc/terms/richter-transformation/), [TP53-mutated (p53-abnormal)](https://onco.cc/terms/tp53-mutated/))
- Diffuse large B-cell type, first treatment: R-CHOP or R-EPOCH chemoimmunotherapy, with venetoclax added in trials; pirtobrutinib or a bispecific antibody in patients unfit for chemotherapy or within trials. ([Rituximab](https://onco.cc/drugs/rituximab/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Prednisone](https://onco.cc/drugs/prednisone/), [R-CHOP (lymphoma chemoimmunotherapy)](https://onco.cc/terms/r-chop/), [Venetoclax](https://onco.cc/drugs/venetoclax/), [Pirtobrutinib](https://onco.cc/drugs/pirtobrutinib/), [Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome](https://onco.cc/trials/nct04623541/))
- Consolidation in responders: Allogeneic stem cell transplant for fit patients with a donor; autologous transplant where chemosensitive and no donor. ([Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [Autologous stem cell transplant (high-dose therapy)](https://onco.cc/technologies/autologous-stem-cell-transplant/))
- Relapsed or chemotherapy-refractory: Clinical trial: bispecific antibodies (epcoritamab, glofitamab), BTK inhibitor with checkpoint inhibitor, CD19 CAR-T, pirtobrutinib; palliative care. ([Pirtobrutinib](https://onco.cc/drugs/pirtobrutinib/), [Acalabrutinib](https://onco.cc/drugs/acalabrutinib/), [CAR-T cell therapy](https://onco.cc/technologies/car-t/), [Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome](https://onco.cc/trials/nct04623541/), [ACP-196 (Acalabrutinib), a Novel Bruton Tyrosine Kinase (BTK) Inhibitor, for Treatment of Chronic Lymphocytic Leukemia, Richter's Syndrome or Prolymphocytic Leukemia](https://onco.cc/trials/nct02029443/))

## State of the art

- Chemoimmunotherapy with allogeneic transplant consolidation is the only route to long-term survival, and reaches a minority.
- 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.
- Richter transformation is a change in a clone rather than a second cancer, and its genetics are its own. Across 86 pathologically proven cases, TP53 disruption was present in 47.1% and MYC abnormality in 26.2%, while the usual drivers of de novo diffuse large B-cell lymphoma were rare or absent.
- Whether the large-cell clone is related to the leukaemic clone matters more than any drug currently does. Clonally unrelated cases had median survival of 62.5 months against 14.2 months for related ones, and less TP53 disruption, 23.1% against 60.0%, so establishing the relationship changes the expected course.
- What prompts the suspicion is one site growing much faster than the rest, new B symptoms, a rising LDH or a PET scan with one area far brighter than the others, and what settles it is a biopsy of that area.

## Open problems

- 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Richter%27s_transformation
- Wikipedia: https://en.wikipedia.org/wiki/Richter%27s_transformation
- NCCN Guidelines: CLL/SLL: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1478

## Connected records

- cancers: [Chronic lymphocytic leukaemia](https://onco.cc/cancers/cll/), [Chronic lymphocytic leukaemia, first treatment](https://onco.cc/cancers/cll-treatment-naive/), [Relapsed or refractory chronic lymphocytic leukaemia](https://onco.cc/cancers/cll-relapsed/)
- biomarkers: [Double-hit and triple-hit: MYC with BCL2 and BCL6 rearrangement](https://onco.cc/biomarkers/double-hit-rearrangement/), [Immunoglobulin and T-cell receptor clonality](https://onco.cc/biomarkers/ig-tcr-clonality/), [TP53 mutation and del(17p)](https://onco.cc/biomarkers/tp53-del17p/)
- technologies: [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [Autologous stem cell transplant (high-dose therapy)](https://onco.cc/technologies/autologous-stem-cell-transplant/), [CAR-T cell therapy](https://onco.cc/technologies/car-t/), [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [Cytogenetics and FISH](https://onco.cc/technologies/cytogenetics-fish/), [FDG PET](https://onco.cc/technologies/fdg-pet/), [Immunoglobulin and T-cell receptor clonality testing](https://onco.cc/technologies/clonality-testing/), [PET/CT](https://onco.cc/technologies/pet-ct/), [T-cell engagers (bispecific)](https://onco.cc/technologies/t-cell-engager/)
- targets: [BTK (Bruton tyrosine kinase)](https://onco.cc/targets/btk/), [CD19](https://onco.cc/targets/cd19/), [CD20](https://onco.cc/targets/cd20/), [CDKN2A](https://onco.cc/targets/cdkn2a/), [MYC](https://onco.cc/targets/myc-gene/), [NOTCH1](https://onco.cc/targets/notch1/), [TP53](https://onco.cc/targets/tp53/)
- pathways: [Clonal evolution & minimal residual disease](https://onco.cc/pathways/clonal-evolution/), [MYC](https://onco.cc/pathways/myc/), [The p53 network (guardian of the genome)](https://onco.cc/pathways/p53-mdm2-axis/)
- terms: [CDKN2A/B homozygous deletion](https://onco.cc/terms/cdkn2a-homozygous-deletion/), [Deauville score and PET-adapted therapy](https://onco.cc/terms/deauville/), [del(17p) / TP53 aberration in CLL](https://onco.cc/terms/del17p-tp53/), [R-CHOP (lymphoma chemoimmunotherapy)](https://onco.cc/terms/r-chop/), [Richter transformation](https://onco.cc/terms/richter-transformation/), [TP53-mutated (p53-abnormal)](https://onco.cc/terms/tp53-mutated/), [Transformation of an indolent lymphoma](https://onco.cc/terms/lymphoma-transformation/), [Transformation: when a slow lymphoma turns into a fast one](https://onco.cc/terms/lymphoma-bio-transformation/)
- key papers: [Biology and treatment of Richter syndrome](https://onco.cc/key-papers/paper-rossi-richter-syndrome-blood-2018/), [WHO classification of haematolymphoid tumours, fifth edition: lymphoid neoplasms](https://onco.cc/key-papers/paper-who-2022-lymphoid-alaggio-leukemia-2022/)
- drugs: [Acalabrutinib](https://onco.cc/drugs/acalabrutinib/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Ibrutinib](https://onco.cc/drugs/ibrutinib/), [Pirtobrutinib](https://onco.cc/drugs/pirtobrutinib/), [Prednisone](https://onco.cc/drugs/prednisone/), [Rituximab](https://onco.cc/drugs/rituximab/), [Venetoclax](https://onco.cc/drugs/venetoclax/)
- trials: [ACP-196 (Acalabrutinib), a Novel Bruton Tyrosine Kinase (BTK) Inhibitor, for Treatment of Chronic Lymphocytic Leukemia, Richter's Syndrome or Prolymphocytic Leukemia](https://onco.cc/trials/nct02029443/), [Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome](https://onco.cc/trials/nct04623541/)

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JSON: https://onco.cc/api/v1/entities/richter-transformation-cll.json