Paraneoplastic Intrahepatic Cholestasis in Supradiaphragmatic Classical Hodgkin Lymphoma Successfully Treated With Brentuximab Vedotin: A Case Report and Review of the Literature

Abstract

Background: Hepatic dysfunction in patients with classical Hodgkin lymphoma (cHL) is of multifactorial aetiology. Prompt evaluation with laboratory tests and imaging methods is sufficient for diagnosis in most cases. Intrahepatic cholestasis and vanishing bile duct syndrome (VBDS) may complicate cHL as rare paraneoplastic phenomena. Liver biopsy provides crucial evidence of cholestasis, and ductopenia, if present, confirms the diagnosis of VBDS. Case Report: We report on a cHL patient that presented with jaundice and bulky mediastinal disease and unfold the therapeutic dilemmas we confronted. Marked hyperbilirubinemia was successfully reversed with brentuximab vedotin (BV) at a dose of 1.2 mg/kg and the patient was subsequently treated with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) at full doses, achieving complete metabolic response. A literature review of intrahepatic cholestasis in cHL is also presented based on currently available data with focus on treatment options and clinicopathologic associations. Conclusion: VBDS and intrahepatic cholestasis are rare and potentially fatal complications of cHL. Their prompt recognition and appropriate treatment can dramatically affect cHL patients' outcome. BV, used at a reduced dose as a bridging therapy, should be considered as a high-priority treatment plan in these challenging cases.

Hodgkin lymphoma associated vanishing bile duct syndrome treated successfully with a brentuximab based regimen

“…8 9 Since first described in 1993, 37 cases of VBDS associated cHL have been reported in the English medical literature. [10][11][12][13][14][15][16][17][18][19][20] Including our case, of the cases with known outcomes, 16 of 35 resulted in short interval death with the majority appearing to have died of liver related complications. In contrast, since 2019 only 3 of 11 cases ended in death.…”

“…A partial metabolic response was achieved with five cycles of the dose reduced to 1.2 mg/kg and then stable disease was seen with another five cycles of the regular dose of 1.8 mg/kg though the patient ultimately had progression of disease on this regimen 19. Finally, Papakonstantinou e t al describe also treating a patient with stage IIb cHL with dose reduced brentuximab as monotherapy for 2 weeks and saw a dramatic improvement in liver function with this allowing initiation of full dose chemotherapy thereafter 20…”

“…While a single case of severe liver injury was reported after seven cycles of full dose brentuximab vedotin in 2019, the incidence of hepatoxicity was low, likely between 0.61% and 1.4% 21 23. Additionally, it has been successfully employed in several other cases of VBDS 17–20. We also avoided vincristine and doxorubicin which would have obvious toxicity due to its metabolism by the liver.…”

“…19 Finally, Papakonstantinou et al describe also treating a patient with stage IIb cHL with dose reduced brentuximab as monotherapy for 2 weeks and saw a dramatic improvement in liver function with this allowing initiation of full dose chemotherapy thereafter. 20 Our main goal in selecting the therapy for this patient was to maximise the chance of cure while minimising treatment related morbidity. The protocol we used, AHOD1331, had shown that the addition of brentuximab to the chemotherapy backbone containing doxorubicin, vincristine, etoposide, cyclphophamide and prednisone (ABVE-PC) results in an outstanding 3-year event-free survival (EFS) of 92%.…”

Paraneoplastic Syndromes in Hodgkin’s Lymphoma

“…Dose-reduced chemotherapy can be used initially to minimize hepatotoxicity, with ursodeoxycholic acid and steroids as an adjunct. Standard chemotherapy regimens can be used once liver function tests have normalized [64].…”