{"entity":{"id":"richter-transformation-cll","kind":"cancer","name":"Richter transformation of chronic lymphocytic leukaemia","aka":["Richter syndrome","Richter's transformation","CLL transformed to diffuse large B-cell lymphoma","Transformed CLL"],"tldr":"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.\n\nStandard 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.\n\nEvery 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.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Richter%27s_transformation","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Richter%27s_transformation"},{"label":"NCCN Guidelines: CLL/SLL","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1478"}],"tags":["subtype-page"],"related":[],"cancers":[],"sections":[],"technologies":["allogeneic-hsct","car-t","pet-ct","t-cell-engager"],"targets":["btk","cd20","cd19","tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["richter-transformation","r-chop","tp53-mutated","del17p-tp53"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"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)"],"standardOfCare":[{"setting":"Diagnosis","approach":"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.","refs":["pet-ct","richter-transformation","tp53-mutated"],"guideline":{"version":"NCCN Guidelines: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1478"}},{"setting":"Diffuse large B-cell type, first treatment","approach":"R-CHOP or R-EPOCH chemoimmunotherapy, with venetoclax added in trials; pirtobrutinib or a bispecific antibody in patients unfit for chemotherapy or within trials.","refs":["rituximab","cyclophosphamide","prednisone","r-chop","venetoclax","pirtobrutinib","nct04623541"],"guideline":{"version":"NCCN Guidelines: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1478"}},{"setting":"Consolidation in responders","approach":"Allogeneic stem cell transplant for fit patients with a donor; autologous transplant where chemosensitive and no donor.","refs":["allogeneic-hsct","autologous-stem-cell-transplant"],"guideline":{"version":"NCCN Guidelines: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1478"}},{"setting":"Relapsed or chemotherapy-refractory","approach":"Clinical trial: bispecific antibodies (epcoritamab, glofitamab), BTK inhibitor with checkpoint inhibitor, CD19 CAR-T, pirtobrutinib; palliative care.","refs":["pirtobrutinib","acalabrutinib","car-t","nct04623541","nct02029443"],"guideline":{"version":"NCCN Guidelines: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1478"}}],"stateOfArt":["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."],"history":[{"year":1928,"title":"Maurice Richter describes reticular cell sarcoma arising in chronic lymphocytic leukaemia","refs":["richter-transformation"]},{"year":2011,"title":"Rossi and colleagues show clonally related transformation carries TP53 and NOTCH1 lesions and a poor outcome","refs":["tp53-mutated"]},{"year":2013,"title":"Richter transformation described on ibrutinib, a mode of BTK inhibitor failure","refs":["ibrutinib"]},{"year":2023,"title":"Pirtobrutinib and bispecific antibodies report activity in Richter cohorts","refs":["pirtobrutinib"]}],"pipeline":["pirtobrutinib","venetoclax","nct04623541","nct02029443","car-t"],"openProblems":["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."],"parent":"cll"},"route":"/cancers/richter-transformation-cll/","neighbours":{"technology":[{"id":"allogeneic-hsct","kind":"technology","name":"Allogeneic stem cell transplantation","route":"/technologies/allogeneic-hsct/"},{"id":"autologous-stem-cell-transplant","kind":"technology","name":"Autologous stem cell transplant (high-dose therapy)","route":"/technologies/autologous-stem-cell-transplant/"},{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"},{"id":"pet-ct","kind":"technology","name":"PET/CT","route":"/technologies/pet-ct/"},{"id":"t-cell-engager","kind":"technology","name":"T-cell engagers (bispecific)","route":"/technologies/t-cell-engager/"}],"target":[{"id":"btk","kind":"target","name":"BTK (Bruton tyrosine kinase)","route":"/targets/btk/"},{"id":"cd19","kind":"target","name":"CD19","route":"/targets/cd19/"},{"id":"cd20","kind":"target","name":"CD20","route":"/targets/cd20/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"term":[{"id":"del17p-tp53","kind":"term","name":"del(17p) / TP53 aberration in CLL","route":"/terms/del17p-tp53/"},{"id":"r-chop","kind":"term","name":"R-CHOP (lymphoma chemoimmunotherapy)","route":"/terms/r-chop/"},{"id":"richter-transformation","kind":"term","name":"Richter transformation","route":"/terms/richter-transformation/"},{"id":"tp53-mutated","kind":"term","name":"TP53-mutated (p53-abnormal)","route":"/terms/tp53-mutated/"}],"drug":[{"id":"acalabrutinib","kind":"drug","name":"Acalabrutinib","route":"/drugs/acalabrutinib/"},{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"ibrutinib","kind":"drug","name":"Ibrutinib","route":"/drugs/ibrutinib/"},{"id":"pirtobrutinib","kind":"drug","name":"Pirtobrutinib","route":"/drugs/pirtobrutinib/"},{"id":"prednisone","kind":"drug","name":"Prednisone","route":"/drugs/prednisone/"},{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"},{"id":"venetoclax","kind":"drug","name":"Venetoclax","route":"/drugs/venetoclax/"}],"trial":[{"id":"nct02029443","kind":"trial","name":"ACP-196 (Acalabrutinib), a Novel Bruton Tyrosine Kinase (BTK) Inhibitor, for Treatment of Chronic Lymphocytic Leukemia, Richter's Syndrome or Prolymphocytic Leukemia","route":"/trials/nct02029443/"},{"id":"nct04623541","kind":"trial","name":"Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome","route":"/trials/nct04623541/"}],"cancer":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"}]}}