Dataset Information

The return of gemtuzumab ozogamicin: a humanized anti-CD33 monoclonal antibody-drug conjugate for the treatment of newly diagnosed acute myeloid leukemia.

ABSTRACT: Through the years gemtuzumab ozogamicin (GO) has moved from a panacea in the treatment of acute myeloid leukemia (AML) to a pariah and back again. Early promise of targeted therapy with accelerated approval in the United States in 2000 gave way to fear over increased toxicity in the absence of efficacy, which subsequently resulted in the drug manufacturer voluntarily withdrawing GO from the market in 2010. We outline the history of GO in terms of initial drug development and early clinical trials that ultimately led the way to GO frontline use in AML based on a series of Phase III studies. Among these studies, we discuss the similarities and differences in terms of dosing, frequency, response rates, and toxicities that ultimately led to the re-approval of GO in 2017 based on efficacy, particularly in patients with core-binding factor (CBF) leukemia. Herein, we also review the clinical efficacy of GO in the frontline treatment of acute promyelocytic leukemia, which is based on either initial patient high-risk disease or potential co-morbidities that preclude the use of arsenic trioxide (ATO). Finally, we assess the current evidence for biomarkers aside from initial cytogenetics that may predict a favorable response to GO.

SUBMITTER: Egan PC

PROVIDER: S-EPMC6254990 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The return of gemtuzumab ozogamicin: a humanized anti-CD33 monoclonal antibody-drug conjugate for the treatment of newly diagnosed acute myeloid leukemia.

Egan Pamela C PC Reagan John L JL

OncoTargets and therapy 20181122

Through the years gemtuzumab ozogamicin (GO) has moved from a panacea in the treatment of acute myeloid leukemia (AML) to a pariah and back again. Early promise of targeted therapy with accelerated approval in the United States in 2000 gave way to fear over increased toxicity in the absence of efficacy, which subsequently resulted in the drug manufacturer voluntarily withdrawing GO from the market in 2010. We outline the history of GO in terms of initial drug development and early clinical trial ...[more]

PMID: 30538495

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

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.

Dataset Information

The return of gemtuzumab ozogamicin: a humanized anti-CD33 monoclonal antibody-drug conjugate for the treatment of newly diagnosed acute myeloid leukemia.

Publications

The return of gemtuzumab ozogamicin: a humanized anti-CD33 monoclonal antibody-drug conjugate for the treatment of newly diagnosed acute myeloid leukemia.

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets