Prevention, recognition, and management of adverse events associated with gemtuzumab ozogamicin use in acute myeloid leu
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REVIEW
Prevention, recognition, and management of adverse events associated with gemtuzumab ozogamicin use in acute myeloid leukemia Jorge E. Cortes1* , Marcos de Lima2, Hervé Dombret3, Elihu H. Estey4, Sergio A. Giralt5, Pau Montesinos6,7, Christoph Röllig8, Adriano Venditti9 and Eunice S. Wang10
Abstract Gemtuzumab ozogamicin (GO), a humanized anti-CD33 monoclonal antibody conjugated to the cytotoxic antibiotic agent calicheamicin, is approved for the treatment of newly-diagnosed CD33 + AML in adults and children ≥ 1 month old, and relapsed or refractory CD33 + AML in adults and children ≥ 2 years old. GO treatment has been associated with an increased risk of hepatotoxicity and hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/ SOS), especially following hematopoietic stem cell transplantation. Other non-specific serious adverse events (SAEs) associated with GO treatment are myelosuppression, bleeding/thrombocytopenia, infusion-related reaction, and tumor lysis syndrome. This report summarizes an expert panel of physicians’ recommendations for the evaluation and management of SAEs following GO, emphasizing the prevention and management of VOD/SOS. Keywords: Acute myeloid leukemia, Adverse events, Gemtuzumab ozogamicin, Treatment management, VOD/SOS Background Gemtuzumab ozogamicin (GO) is an antibody drug conjugate comprising a CD33-directed monoclonal antibody covalently linked to the cytotoxic agent N-acetyl gamma calicheamicin. The CD33 antigen is expressed on the vast majority of myeloid leukemic blasts and immature normal cells of myelomonocytic lineage, but not on normal hematopoietic stem cells [1–3]. GO was granted accelerated approval by the United States (US) Food and Drug Administration (FDA) in 2000 as monotherapy (9 mg/ m2 repeated after 14 days on approximately 28-day cycles) for patients ≥ 60 years of age with CD33-positive (CD33 +) acute myeloid leukemia (AML) in first relapse and who were not candidates for standard chemotherapy [4]. Approval was granted based on three phase II studies in which the administration of single-agent GO (9 mg/m2 *Correspondence: [email protected] 1 Georgia Cancer Center, 1410 Laney Walker Road, CN2116, Augusta, GA 30912, USA Full list of author information is available at the end of the article
on days 1 and 14 of induction) resulted in a 26% rate of complete remission with (CR) and without (CRp) platelet recovery in patients > 60 years of age. Myelosuppression and hepatotoxicity were the most serious toxicities reported in these early clinical trials. GO was voluntarily withdrawn from the market in 2010 after a post-approval trial (Southwest Oncology Group [SWOG] S0106) failed to confirm benefit in patients randomized to GO (6 mg/m2 on day 4) plus daunorubicin (DNR, 45 mg/m2 per day on days 1, 2, and 3) and cytarabine (AraC; 100 mg/m2 per day by continuous infusion on days 1–7) versus DNR (60 mg/m2) plus AraC alone [5]. The SWOG S0106 study was terminated early by the data monitoring committee due to a higher incidence of
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