Gemtuzumab ozogamicin (Mylotarg™) is infrequently associated with sinusoidal obstructive syndrome/veno-occlusive disease

Background: Germuzumab ozogamicin (GO) is approved for the treatment of older adults with acute myeloid leukemia in first relapse. Several reports have suggested an association between GO administration and hepatic veno-occlusive disease (VOD), which has recently been termed sinusoidal obstructive syndrome (SOS). However, the majority of these studies were done in patients who had undergone high-dose therapy with stem cell transplantation or when GO was administered in combination with other cytotoxic chemotherapy. Patients and methods: We performed a retrospective review of all patients treated at our institution with single-agent GO, either as initial therapy or in the relapsed and refractory setting. All patients were planned to receive GO 9 mg/m(2) in two doses, 14 days apart. We reviewed liver function tests before and after administration and analyzed hepatic injuries in the context of patients' other comorbid conditions. Patients were classified as experiencing liver toxicity if their liver function(s) abnormality lasted for >7 days, as documented by repeated serum studies. Results: Forty-seven patients were analyzed. Response rate (27.2%) and median duration of response (6 months) were comparable to other reports. All patients were assessable for liver toxicity, of which 23 (48%) had elevation of at least one of their liver function tests (alanine aminotransferase, aspartate aminotransferase, total bilirubin or alkaline phosphatase). Elevations in liver function test(s) were noted at a median of 14 days (range 7-175 days). Eight patients had other comorbid conditions that could explain their liver abnormality, making the incidence of direct GO-induced liver injury 31%. However, only one patient had radiographic and clinical evidence suggesting SOSVOD. Conclusions: When administered using the recommended dose and schedule, GO has little association with VODSOS if given as a single agent. In this retrospective review, the incidence of GO-related SOSVOD is as low as 2%.