Mylotarg(TM) (gemtuzumab ozogamicin) therapy is associated with hepatic venoocclusive disease in patients who have not received stem cell transplantation

BACKGROUND. Mylotarg (TM) (Wyeth-Ayerst Laboratories, St. Davids, PA] is th e brand name for a calicheamicin-conjugated humanized anti-CD33 monoclonal antibody (gemtuzumab ozogamicin, CMA-676) and has been approved recently fo r the treatment of a subset of elderly patients who have relapsed acute mye loid leukemia (AML). Mylotarg is associated with an incidence of approximat ely 20% Grade 3 or 4 hyperbilirubinemia and liver transaminitis in this pat ient population. Hepatic venoocclusive disease (VOD) has been reported in p atients who have undergone stem cell transplantation (SCT) after Mylotarg t herapy. Outside of the SCT setting, VOD has been associated very rarely wit h cytotoxic therapy. METHODS. The authors assessed the incidence of VOD in 119 patients who were receiving Mylotarg-containing non-SCT regimens. VOD was diagnosed through the use of standard Seattle and Baltimore criteria. RESULTS. A cohort of 119 (61 previously untreated, 58 with relapsed disease ) patients with AML (92 patients), advanced myelodysplastic syndrome (25 pa tients), or chronic myeloid leukemia in blast phase (2 patients), received Mylotarg-based regimens. Fourteen (12%) developed VOD. The diagnosis of VOD was supported by histology in 2 patients and radiologic studies in a furth er 10 patients. Five (36%) of 14 patients with VOD had received no prior an tileukemic cytotoxic therapy, including 2 patients who received single-agen t Mylotarg therapy. CONCLUSIONS. Mylotarg was shown to be associated with the development of po tentially fatal VOD in patients with leukemia who had not received SCT. VOD occured when Mylotarg was used either as a single agent or when it was giv en with other cytotoxic agents. VOD occured in Mylotarg-treated patients wh o had received no prior cytotoxic therapy. The current study concluded that risk factors for VOD should be assessed when considering Mylotarg therapy, and that attempts to avoid and treat VOD are warranted in patients who rec eive Mylotarg therapy. (C) 2001 American Cancer Society.