Abstract
Simple SummaryGemtuzumab Ozogamicin (GO) is a drug approved for the treatment of acute myeloid leukemia (AML). It targets leukemic cells that express the CD33 molecule on their surface and brings the toxic agent calicheamicin inside the cell to kill it. Several studies have shown that AML patients can benefit of the addition of GO to chemotherapy during induction regimens, pre- and post-transplantation. Moreover, some disease features have been addressed or are under investigation for their capacity to predict response to GO, with the future aim of selecting AML patients that can mostly benefit of GO treatment.Acute myeloid leukemia (AML) is a complex hematological malignancy characterized by genetic and clinical heterogeneity and high mortality. Despite the recent introduction of novel pharmaceutical agents in hemato-oncology, few advancements have been made in AML for decades. In the last years, the therapeutic options have rapidly changed, with the approval of innovative compounds that provide new opportunities, together with new challenges for clinicians: among them, on 1 September, 2017 the Food and Drug Administration granted approval for Gemtuzumab Ozogamicin (GO) in combination with daunorubicin and cytarabine for the treatment of adult patients affected by newly diagnosed CD33+ AML. Benefits of GO-based regimens were also reported in the pre- and post-transplantation settings. Moreover, several biomarkers of GO response have been suggested, including expression of CD33 and multidrug resistance genes, cytogenetic and molecular profiles, minimal residual disease and stemness signatures. Among them, elevated CD33 expression on blast cells and non-adverse cytogenetic or molecular risk represent largely validated predictors of good response.
Highlights
Many patients affected by acute myeloid leukemia (AML) benefit of chemotherapy regimens and hematopoietic stem cell transplant (HSCT)
In this review we summarize the clinical results obtained on CD33 targeting by Gemtuzumab Ozogamicin (GO) in Acute myeloid leukemia (AML) as single agent and in combination with chemotherapy, its potential benefit pre- and post-transplantation and we discuss the predictive biomarkers of therapy response
Data based on clinical experience showed that GO can be safely added (i) to a busulfan/cyclophosphamide conditioning regimen before alloSCT in children and adolescents affected by poor-risk AML [69]; (ii) to fludarabine and cytarabine (FLA) before HSCT
Summary
Many patients affected by acute myeloid leukemia (AML) benefit of chemotherapy regimens and hematopoietic stem cell transplant (HSCT). Different types of immunotherapy have been developed, including antibody drug conjugates (ADCs) [1,2]. The advances of ADCs is to combine the specificity of a monoclonal antibody with the therapeutically benefits of chemotherapy agents [3]. CD33 became an ideal target for the development of new ADCs due to the fact that its expression is common on the surface of AML blast cells and almost absent in normal pluripotent hematopoietic stem cells. In this review we summarize the clinical results obtained on CD33 targeting by GO in AML as single agent and in combination with chemotherapy, its potential benefit pre- and post-transplantation and we discuss the predictive biomarkers of therapy response
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