Version July 2025
ABVD: doxorubicin, bleomycin, vinblastine, and dacarbazine; BTK: Bruton tyrosine kinase; CAR: chimeric antigen receptor; CLL: chronic lymphocytic leukemia; CR: complete remission; da-EPOCH-R: dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab; DLBCL: diffuse large B cell lymphoma; FDG: fluorodeoxyglucose; HCT: hematopoietic cell transplantation; HL: Hodgkin lymphoma; PET/CT: positron emission tomography with computed tomography; R-CHOP: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; SLL: small lymphocytic leukemia.
* RT should be suspected in patients with a sudden clinical deterioration, characterized by a marked increase in lymphadenopathy at one or more sites, splenomegaly, and/or worsening "B" symptoms (ie, fever, night sweats, weight loss). Laboratory studies may demonstrate an elevated serum level of lactate dehydrogenase, 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, acalabrutinib, zanubrutinib, and pirobrutinib. Patients who develop RT while taking the BCL2 inhibitor venetoclax can proceed with standard anthracycline-based combination chemotherapy.
◊ There are limited data regarding the use of more modern treatment regimens, such as the combination of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (AVD), and many patients may not be able to tolerate these intensive regimens. Although better tolerated, there is no experience with nivolumab plus AVD in this setting.
§ 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 plus R-CHOP) rather than standard chemotherapy. The BTK inhibitor should not be stopped abruptly.
¥ For patients who are candidates and have refractory disease, CAR-T cell therapy is the most promising treatment option to achieve remission and potentially bridge to allogeneic HCT. Allogeneic HCT is appropriate for eligible patients after CAR-T cell therapy since responses to CAR-T cell therapy in RT appear to be less durable than those seen in de novo DLBCL.
‡ 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.
