Clinical outcomes of gemtuzumab ozogamicin for relapsed acute myeloid leukemia: single-institution experience

Hosono, Naoko; Ookura, Miyuki; Araie, Hiroaki; Morita, Minoru; Itoh, Kazuhiro; Matsuda, Yoshiki; Yamauchi, Takahiro

doi:10.1007/s12185-020-03023-4

Cited by 8 publications

(4 citation statements)

References 20 publications

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“…The overall response rate was 52.3% and that was above the literature data. In the study of Hosono et al., all patients died in the first year, whereas in our study, 3 patients were alive in the first year [17] . Similar to the literature, response rates decreased the longer the follow-up.…”

Section: Discussioncontrasting

confidence: 62%

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Use of gemtuzumab ozogamicin in relapsed refractory acute myeloid leukemia: Multi-center real life data from Turkey

Küçükdiler

Yavaşoğlu

Selim

et al. 2021

Leukemia Research Reports

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Section: Discussioncontrasting

confidence: 62%

“…Six patients responded to treatment and the overall response rate was 31.6% in this study. The most common adverse event was febrile neutropenia(84%) [17] .…”

Section: Discussionmentioning

confidence: 99%

Use of gemtuzumab ozogamicin in relapsed refractory acute myeloid leukemia: Multi-center real life data from Turkey

Küçükdiler

Yavaşoğlu

Selim

et al. 2021

Leukemia Research Reports

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“…A study showed that when GO was administered as a single agent, it appeared to be an effective option for treating relapsed AML, with a 31.6% response rate [19]. The same conclusion was reached by another study, which showed that GO had an antileukemic effect in AML patients with NPM1 mutation and significantly reduced the cumulative incidence of recurrence rate.…”

Section: Gemtuzumab Ozogamicin Pharmacokineticsmentioning

confidence: 74%

Gemtuzumab Ozogamicin in Acute Myeloid Leukemia: Efficacy, Toxicity, and Resistance Mechanisms—A Systematic Review

Collados-Ros,

Muro,

Legaz

2024

Biomedicines

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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.

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“…It has been shown by both phase I/II clinical trials and retrospective studies that GO alone or in combination with various regimens was safe and effective in patients with the first relapse of AML [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. There are limited real-world data about the effect of GO on clinical outcomes in patients with recurrent AML [ 22 , 23 ]. Moreover, the use of GO in multiple relapses of AML patients has not yet been extensively investigated.…”

Section: Introductionmentioning

confidence: 99%

The Use of Gemtuzumab Ozogamicin as Salvage Therapy in Patients with Acute Myeloid Leukemia: A Monocentric Real-World Experience

Açar

Güvenç

2023

Medicina

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Background and Objectives: Relapsed or refractory acute myeloid leukemia (r/r AML) is a disease with a poor prognosis. Limited treatment options are available in r/r AML. Here, we administered gemtuzumab ozogamicin (GO) as salvage therapy in twenty-four patients with r/r AML. The aim of the study was to determine the role of GO in r/r AML in real life. Material and Methods: This retrospective observational study recruited 24 adult patients with diagnosed r/r AML from 2018 to 2022. Twenty-four patients with r/r AML were treated with GO. GO treatment was used as monotherapy in 23 patients and in combination with cytarabine in 1 patient. At the time of diagnosis, the risk status of all patients was determined as favorable, intermediate, or adverse according to the 2017 ELN AML guidelines. Results: The median follow-up was 44.3 (13–144) months. Fifteen (62.5%) of the twenty-four patients were in the intermediate-risk cytogenetics group and nine (37.5%) were in the favorable cytogenetics group. The most common adverse events included nausea/vomiting in 79.17% (n = 19) of patients, headache in 62.50% (n = 15), elevated LFTs in 37.50% (n = 9), febrile neutropenia in 25% (n = 6), and bleeding in 25% (n = 6). The most common cause of death was infection. The most common causes of mortality were septic shock, accounting for 33.3% (n = 8) of deaths, and opportunistic lung infection, accounting for 12.5% (n = 3) of deaths. Acute infusion-related toxicities associated with GO were usually transient and, in most cases, responded to the standard of care treatment. After treatment with GO, 16.6% (n = 4) of patients achieved MLFS and 37.5% (n = 9) achieved CR. The overall response rate was 54.1%. The median overall survival time of the patients was 44 months (37.8–50.2 months). Disease-free survival was 22 months (0–48.6 months). The 5-year survival rate was 33%. Conclusions: A low dose of GO improved the overall survival and disease-free survival in r/r AML patients. GO treatment had a positive safety profile in terms of toxicity.

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Clinical outcomes of gemtuzumab ozogamicin for relapsed acute myeloid leukemia: single-institution experience

Cited by 8 publications

References 20 publications

Use of gemtuzumab ozogamicin in relapsed refractory acute myeloid leukemia: Multi-center real life data from Turkey

Use of gemtuzumab ozogamicin in relapsed refractory acute myeloid leukemia: Multi-center real life data from Turkey

Gemtuzumab Ozogamicin in Acute Myeloid Leukemia: Efficacy, Toxicity, and Resistance Mechanisms—A Systematic Review

The Use of Gemtuzumab Ozogamicin as Salvage Therapy in Patients with Acute Myeloid Leukemia: A Monocentric Real-World Experience

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