Single Agent Brentuximab As Bridging Therapy for Hodgkin Lymphoma Patients with Hepatic Impairment

Background: Patients with Hodgkin lymphoma (HL) can rarely present with hepatic impairment which may preclude administration of definitive therapy (ABVD, or other cytotoxic regimens). Brentuximab Vedotin (BV) is an antibody drug conjugate directed at CD30 and is approved for the treatment of refractory HL after failure of at least two prior chemotherapy regimens or after failure of autologous stem cell transplant. We report our experience of patients presenting with advanced stage HL and moderate to severe hepatic impairment who were unfit to receive ABVD therapy.

Methods: Patients with HL, unfit to receive definitive ABVD therapy, treated with BV between 5/2014 and 5/2015, were included in the study. Patient charts were reviewed for administration of BV; and those with baseline hepatic impairment were included in the study. Structured forms were used to abstract relevant clinical data.

Results: Five patients were included in this study; median age 38 (range 27-71 years); all were male. Three were Hispanic and two were African-American. Two had known history of human immunodeficiency virus-1 (HIV) infection. All had stage 4 disease at presentation, 3 had bone marrow involvement, while four reported 'B' symptoms. All had hepatocellular and cholestatic pattern of liver injury on admission laboratory exam, and were not considered candidates for standard ABVD therapy. Two patients had HIV infection controlled by antiviral therapy. Liver biopsy showed hepatic HL infiltrate in two patients, VBDS in two patients, and suspected drug induced liver injury (DILI) in one patient. Patients with intrahepatic HL and VBDS had not received any therapy for HL; the patient with DILI had recently received therapy with gemcitabine. Due to concern for potential ABVD-related toxicity, all patients were treated with BV. Therapy was continued every 3 weeks till normalization of serum bilirubin to <1 mg/dL; this was achieved in all patients. Three patients received 3 doses of BV, while 2 patients received 5 doses. BV therapy was initially given at reduced dose (1.2 mg/kg) and dose was increased to the standard 1.8 mg/kg once serum bilirubin levels started to trend down and reached <5 mg/dl. Median time to halving of serum bilirubin from pre-treatment value was 15 (range, 8- 58 days. Median time to normalization of serum bilirubin (<1 mg/dL) was 64 (range, 41and 154 days. Three patients demonstrated partial response to BV and were switched to ABVD therapy after liver function normalized. Two patients had mixed response to BV and multi-agent therapy (ABVD, and AVD with BV respectively) was initiated once liver function normalized. There were no serious adverse effects of therapy with BV.

Conclusions: Treatment with BV provided successful bridging to definitive chemotherapy in patients with HL with hepatic involvement. In HL patients, liver biopsy may help distinguishing liver injury related to HL, requiring aggressive chemotherapy, from liver injury related to HL treatment, which necessitates alternative regimens. BV can successfully be used as a bridging therapy in advanced HL patients presenting with liver injury who may be unfit to receive more cytotoxic chemotherapy. This was seen in both HIV negative and positive patients. Further studies to establish the safety and efficacy of BV in this scenario is warranted.