Treatment of Richter transformation

CLL: chronic lymphocytic leukemia; SLL: small lymphocytic leukemia; DLBCL: diffuse large B cell lymphoma; HL: Hodgkin lymphoma; RT: Richter transformation; BTK: Bruton tyrosine kinase; ABVD: doxorubicin, bleomycin, vinblastine, and dacarbazine; CR: complete remission; R-CHOP: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; da-EPOCH-R: dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab; HCT: hematopoietic cell transplantation; FDG: fluorodeoxyglucose; PET/CT: positron emission tomography with computed tomography.
* RT should be suspected in patients with a sudden clinical deterioration, characterized by a marked increase in lymphadenopathy at one or more sites, splenomegaly, worsening "B" symptoms (ie, fever, night sweats, weight loss). Laboratory studies may demonstrate an elevated serum level of lactate dehydrogenase (LDH), anemia, and thrombocytopenia.
¶ We suggest using whole body FDG-PET/CT to determine the preferred biopsy site. If possible, the site of greatest FDG avidity should be biopsied.
Δ BTK inhibitors include ibrutinib and acalabrutinib. Patients who develop RT while taking the BCL2 inhibitor venetoclax can proceed with standard anthracycline-based combination chemotherapy.
◊ Patients who develop DLBCL RT while on a BTK inhibitor may have particularly poor outcomes, and these patients should be referred for clinical trials or considered for combination therapy that incorporates another targeted therapy (eg, venetoclax) rather than standard chemotherapy. The BTK inhibitor should not be stopped abruptly.
§ Observation until progression is an acceptable alternative to consolidation with transplant for those who achieve a CR after initial anthracycline-based combination chemotherapy if the DLBCL variant RT is clonally unrelated to the prior CLL, or if they are diagnosed simultaneously. If clonal relationship cannot be determined (as is common in clinical practice), patients with DLBCL variant who have not received therapy for CLL prior to RT and achieve CR after initial anthracycline-based combination chemotherapy can do well without transplant consolidation.