Dataset Information

Effect and safety of gemtuzumab ozogamicin for the treatment of patients with acute myeloid leukaemia: a systematic review protocol.

ABSTRACT:

Introduction

Acute myeloid leukaemia (AML) is a type of cancer in which the bone marrow makes abnormal myeloblasts (a type of white blood cell), red blood cells or platelets. Gemtuzumab ozogamicin (GO) holds promise as a new agent that also could be efficacious in newly diagnosed AML with acceptable toxicity. This paper describes the design of a protocol to conduct a systematic review of published studies assessing GO for the treatment of AML.

Method and analysis

We will conduct a systematic review of randomised controlled trials that investigate the effect and safety of GO for the treatment of patients with AML. We will search for any eligible articles from selected electronic databases. We will follow the Preferred Reporting Items for Systematic reviews and Meta-Analysis for study selection and reporting. We will use The Cochrane Handbook for Systematic Reviews of Interventions and Meta-Analysis as guidance to select eligible studies. All data will be extracted using a standardised data extraction form.

Ethics and dissemination

There was no patient involved in this study, therefore no ethical consideration is needed. The findings of this study will be disseminated in a peer-reviewed journal and any relevant conference presentation.

Prospero registration number

CRD42019123286.

SUBMITTER: Muhamad NA

PROVIDER: S-EPMC7299015 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

Effect and safety of gemtuzumab ozogamicin for the treatment of patients with acute myeloid leukaemia: a systematic review protocol.

Muhamad Nor A NA Mohd Dali Nor S NS Mohd Yacob Aliza A Kassim Mohd S A MSA Lodz Noor A NA Abdul Wahid S F SF Aris Tahir T

BMJ open 20200615 6

<h4>Introduction</h4>Acute myeloid leukaemia (AML) is a type of cancer in which the bone marrow makes abnormal myeloblasts (a type of white blood cell), red blood cells or platelets. Gemtuzumab ozogamicin (GO) holds promise as a new agent that also could be efficacious in newly diagnosed AML with acceptable toxicity. This paper describes the design of a protocol to conduct a systematic review of published studies assessing GO for the treatment of AML.<h4>Method and analysis</h4>We will conduct a ...[more]

PMID: 32540885

Similar Datasets

Project description:BackgroundBased on the results from the ALFA-0701 study, gemtuzumab ozogamicin (GO) has been approved by the European Medicine Agency and by the Italian Drug Agency for the first line treatment of de novo acute-myeloid leukemia (AML). In this analysis, we assessed the cost-effectiveness of GO in combination with daunorubicin and cytarabine (DA), vs DA alone, adopting the perspective of the Italian National Health Service.MethodsFor this analysis, a cohort state transition model was developed. The model was designed to capture health states and events that occur throughout the entire disease course and that impact costs and outcomes. The ALFA-0701 study was the main source of clinical data for this analysis. In the model, patients had the same baseline characteristics and experienced the same clinical improvements as in the ALFA-0701 study. Economic data (resource consumption and unit costs) were adapted to reflect expenditure for the Italian National Health Service. Utilities per health state and disutilities due to adverse events were based on the literature and on the general population for those functionally cured. A lifetime horizon was adopted, with both costs and outcome being discounted of 3.0%, annually. Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of results.ResultsIn the base case (lifetime horizon; primary source of data: study ALFA-0701; perspective: Italian National Health Service; discount rate on costs and outcomes: 3.0%), GO + DA was more effective DA both in terms of life-year (LY) survival (6.42 LY vs 5.75 LY, respectively) and quality-of-life adjusted survival (4.69 QALY vs 4.19 QALY, respectively). The overall costs were almost similar in the two groups (slightly lower with GO + DA than with DA; €162,424 and €162,708, respectively). The use of GO increased the costs of drug therapy but saved costs of relapse and costs associated with transplantation (HSCT).ConclusionsIf results of the ALFA-0701 study are applied to the Italian healthcare environment, then gemtuzumab ozogamicin, in combination with daunorubicin and cytarabine, would clinical outcomes and reduce lifetime costs, compared with daunorubicin and cytarabine alone for the first line treatment of de novo AML.Trial registrationNot applicable.

Project description:Acute myeloid leukemia (AML) is a diverse group of leukemias characterized by the uncontrolled proliferation of clonal neoplastic hematopoietic precursor cells with chromosomal rearrangements and multiple gene mutations and the impairment of normal hematopoiesis. Current efforts to improve AML outcomes have focused on developing targeted therapies that may allow for improved antileukemic effects while reducing toxicity significantly. Gemtuzumab ozogamicin (GO) is one of the most thoroughly studied molecularly targeted therapies in adults. GO is a monoclonal antibody against CD33 IgG4 linked to the cytotoxic drug calicheamicin DMH. The use of GO as a chemotherapeutic agent is not generalized for all patients who suffer from AML, particularly for those whose health prevents them from using intensive conventional chemotherapy, in which case it can be used on its own, and those who have suffered a first relapse, where its combination with other chemotherapeutic agents is possible. This systematic review aimed to comprehensively evaluate GO, focusing on its molecular structure, mode of action, pharmacokinetics, recommended dosage, resistance mechanisms, and associated toxicities to provide valuable information on the potential benefits and risks associated with its clinical use. A systematic review of eight scientific articles from 2018 to 2023 was conducted using PRISMA analysis. The results showed that GO treatment activates proapoptotic pathways and induces double-strand breaks, initiating DNA repair mechanisms. Cells defective in DNA repair pathways are susceptible to GO cytotoxicity. GO has recommended doses for newly diagnosed CD33+ AML in combination or as a single agent. Depending on the treatment regimen and patient status, GO doses vary for induction, consolidation, and continuation cycles. Multidrug resistance (MDR) involving P-glycoprotein (P-gp) is associated with GO resistance. The overexpression of P-gp reduces GO cytotoxicity; inhibitors of P-gp can restore sensitivity. Mitochondrial pathway activation and survival signaling pathways are linked to GO resistance. Other resistance mechanisms include altered pharmacokinetics, reduced binding ability, and anti-apoptotic mechanisms. GO has limited extramedullary toxicity compared to other AML treatments and may cause hepatic veno-occlusive disease (HVOD). The incidence of hepatic HVOD after GO therapy is higher in patients with high tumor burden. Hematological side effects and hepatotoxicity are prominent, with thrombocytopenia and neutropenia observed. In conclusion, GO's reintroduction in 2017 followed a thorough FDA review considering its altered dose, dosing schedule, and target population. The drug's mechanism involves CD33 targeting and calicheamicin-induced DNA damage, leading to apoptosis and resistance mechanisms, including MDR and survival signaling, which impact treatment outcomes. Despite limited extramedullary toxicity, GO is associated with hematological side effects and hepatotoxicity.

Dataset Information

Effect and safety of gemtuzumab ozogamicin for the treatment of patients with acute myeloid leukaemia: a systematic review protocol.

Introduction

Method and analysis

Ethics and dissemination

Prospero registration number

Publications

Effect and safety of gemtuzumab ozogamicin for the treatment of patients with acute myeloid leukaemia: a systematic review protocol.

Similar Datasets

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