Gemtuzumab Ozogamicin After Allogeneic Stem Cell Transplantation for Acute Leukemia

Abstract

AbstractAbstract 1970Controversy abounds that anti-CD33 immunoconjugate, genutuzumab ozogamicin (GO) is really effective or not as a treatment for relapsed acute myeloid leukemia (AML). Consequently, GO is now commercially available in Japan, but not in USA or Europe. In this study, we have retrospectively analyzed the clinical impact of GO therapy as salvage or maintenance setting after allogeneic hematopoietic stem cell transplantation (allo-HSCT).During last 5 years, GO was given to 19 patients with AML as salvage therapy for disease recurrence (n = 15 patients) or maintenance therapy (n = 4 patients) after allo-HSCT in our institution. Clinical characteristics of these 19 patients are summarized (see Table): Median age was 44 years (range, 21–70 years). GO was basically administered at a dose of 3 mg/m2. The median cycle of GO therapy was 3 cycles (range, 1–12 cycles) and 3 cycles (range, 1–4 cycles) as salvage and maintenance therapy, respectively. GO was administered at a median of 205 days after allo-HSCT (range, 38–3,111 days) in the setting of salvage therapy, while as maintenance therapy, patients with high risk AML received GO as early as 29 days after allo-HSCT (range, 24–71 days).Two of 15 patients with recurrent disease achieved complete remission and 4 patients showed partial response (>50% decrease of bone marrow blast percentage). Thus, a total of 6 patients (40%) exhibited initial response to GO. However, 5 patients of them developed irreversible hepatic veno-occulusive disease (VOD) and eventually died at median of 146 days after GO therapy (range, 9–206 days). In view of 4 patients with maintenance therapy, 1 patient have faced to the subsequent disease relapse but no patients developed severe adverse effects including hepatic VOD and all patients are currently alive, albeit short follow-up. This small study demonstrates that GO offers an alternative tool for rescuing relapsed AML after allo-HSCT, but increases the risk of developing life-threatening hepatic VOD. Thus, further clarification is needed regarding which patients to treat with GO and at what dose of GO.TableClinical characteristics of 19 patients with GO for the treatment of relapse or maintananceNoAge/sexDiagnosisType of transplantIndication of GODose of GOInterval between transplant to GO (days)Subsequent allogeneic transplant after GO (Yes or No, interval between GO and transplant, days)Concomitant therapyRespnseRelapse after GOOutcomeSurvival after GO (days)Causes of death160/FMDS overt leukemiaRPBSCTRelapse3mgx399NoDLINRN/ADead31GVHD/fungal infection254/MAML M6UBMTRelapse3mgx33,111NoNoNRN/ADead44Relapse335/FAML M2RBMTRelapse9mgx2192NoNoPRN/ADead159VOD444/MAML M2RBMTRelapse9mgx144NoNoPRN/ADead9VOD531/MAML M1UBMTRelapse3mgx12264Yes, 310NoNRN/ADead557Relapse640/FAML M2UBMTRelapse3mgx3312NoNoNRN/ADead55Relapse725/MAML M6RBMTRelapse3mgx21,735Yes, 30NoNRN/ADead214Sepsis857/FAML M2UBMTRelapse3mgx6354NoNoNRN/ADead27Fungal infection958/MMDS overt leukemiaUBMTRelapse3mgx6205Yes, 175NoCRN/ADead206VOD1049/MAML M1UBMTRelapse3mgx367Yes, 94NoNRN/ADead147MOF1169/MMDS overt leukemiaUBMTRelapse3mgx1416NoNoNRN/ADead38Relapse1233/FAML M2UBMTRelapse3mgx4154Yes, 89NoCRN/ADead146VOD1328/FAML M5RBMTRelapse3mgx5257Yes, 84NoPRN/AAlive142+1469/FAML M2CBSCTRelapse3mgx138Yes, 29AZAPRN/ADead54VOD1570/MAML M1UBMTRelapse3mgx3123NoNoNRN/AAlive238+1621/FAML M1UBMTMaintenance3mgx171NoAZAN/AYesAlive126+1758/FMDS overt leukemiaRPBSCTMaintenance3mgx232NoNoN/ANoAlive109+1838/FMDS overt leukemiaRPBSCTMaintenance3mgx426NoNoN/ANoAlive135+1931/MAML M5RPBSCTMaintenance3mgx424NoAZAN/ANoAlive112+Abbreviations: M=male; F=female; MDS=myelodysplastic syndrome; AML=acute myeloid leukemia; UBMT=unrelated bone marrow transplantation; RPBSCT=related peripheral blood stem cell transplantation; RBMT=related bone marrow transplantation; UBMT=unrelated bone marrow transplantation; GO=Gemtuzumab Ozogamicin; DLI=donor lymphocyte infusion; AZA=azacitidine; NR=no response; PR=partial remision; CR=complete remission; GVHD=graft-versus-host disease; VOD=hepatic veno-occulusive disease; MOF=mutiorgans failure. Disclosures:No relevant conflicts of interest to declare.