A Phase I/II Trial of the Combination of Azacitidine and Gemtuzumab Ozogamicin for Treatment of Relapsed Acute Myeloid Leukemia

Medeiros, Bruno C.; Tanaka, Tiffany; Balaian, Larisa; Bashey, Asad; Guzdar, Amy; Li, Hongying; Messer, Karen; Ball, Edward D.

doi:10.1016/j.clml.2018.02.017

Cited by 33 publications

(29 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In three patients with primary resistance to standard chemotherapy regimens ("FLAG" or azacitidine), poor performance status and respiratory or acute kidney failure, GO monotherapy was treatment due to the primary resistance and poor performance status. At the next step, two of our patients were switched to combined Gemtuzumab ozogamicin plus Azacitidine (GO+Aza) treatment due to the ability of the latter to potentiate the efficacy of GO and overcome resistance to GO [6,7]. CD33 blast cell positivity was obligatory for including the patients in this treatment plan.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Rapid Efficacy of Gemtuzumab Ozogamicin in Refractory AML Patients with Pulmonary and Kidney Failure

Zaytsev

Girshova

Иванов

et al. 2020

Biology

View full text Add to dashboard Cite

Objectives: To the best of our knowledge, data from Gemtuzumab ozogamicin in Acute Myeloid Leukemia (AML) patients with failure of organ functions and poor performance status are extremely lacking. Moreover, the fast recovery from organ failure, after Gemtuzumab ozogamicin administration, has never been reported. This study aimed to demonstrate the efficacy and rapid response of Gemtuzumab ozogamicin in refractory acute myeloid leukemia (AML) patients with pulmonary and kidney failure and poor performance status. Three refractory AML patients, with organ dysfunction, are described. One patient was pre-treated with intensive chemotherapy, and two other patients progressed during Azacitidine treatment. Two patients had respiratory failure grade 2 and one patient suffered from acute kidney insufficiency. Two patients were highly febrile with an elevated C-Reactive Protein (CRP) level. The WHO performance status of three was measured in all patients. Gemtuzumab ozogamicin administration was performed in three patients, followed by a further switch to Gemtuzumab ozogamicin + Azacitidine or "7+3" treatment. Results: Gemtuzumab ozogamicin administration resulted in abrupt fever cessation in two febrile patients simultaneously with a rapid decrease in CRP level and fast resolution of respiratory failure. Recovery of kidney function was noticed rapidly in patients with renal insufficiency. The WHO performance status was elevated in all three patients. No adverse grade II-III effects were noticed. Further treatment made two patients eligible for intensive chemotherapy, one patient underwent allogeneic stem cell transplantation, and the patient with kidney failure obtained complete remission. Conclusions: Gemtuzumab ozogamicin therapy appeared to be safe and highly efficacious in relapsed/refractory AML patients with organ dysfunction, like pulmonary or renal failure and poor performance status, and may contribute to rapid recovery from organ failures.Biology 2020, 9, 28 2 of 8 Relapsed and refractory AML (10-40% of AML) represents the most common group of AML patients with organ dysfunction and poor outcomes [3].Low toxicity of Gemtuzumab ozogamicin (GO) seems to provide a new, promising option for the treatment of highly compromised patients. Amadori et al. reported the results of the GIMEMA trial of GO versus best supportive care in the treatment of unfit for intensive chemotherapy patients in a front-line setting [4]. The toxicity of GO was comparable to best supportive care, whereas a statistically significant increase in overall survival was shown in the GO arm. Moreover, GO has been shown to be an efficacious treatment in relapse/refractory AML patients [5,6]. However, significant organ dysfunction was the exclusion criterion in all these trials. To the best of our knowledge, data of GO in AML patients with organ failure are lacking.Here, we describe three patients with refractory CD 33+ AML and organ failures who benefited from GO use. All of them had uncontrolled leukemic overgrowth. The WHO performance status got ...

show abstract

Section: Discussionmentioning

confidence: 99%

“…The toxicity of GO was comparable to best supportive care, whereas a statistically significant increase in overall survival was shown in the GO arm. Moreover, GO has been shown to be an efficacious treatment in relapse/refractory AML patients [5,6]. However, significant organ dysfunction was the exclusion criterion in all these trials.…”

mentioning

confidence: 99%

Rapid Efficacy of Gemtuzumab Ozogamicin in Refractory AML Patients with Pulmonary and Kidney Failure

Zaytsev

Girshova

Иванов

et al. 2020

Biology

View full text Add to dashboard Cite

show abstract

“…These data are very similar to those obtained by administration of GO alone at higher doses, 9 mg/m 2 given twice . Therefore, additional studies are required to determine the optimal schedule and dose of GO in combination with azacytidine 1 …”

Section: The Mmt Approachmentioning

confidence: 99%

“…[191][192][193] Based on these evidence, a phase I/II trial based on the combination of GO and azacytidine 1 (Combination N, Figure 4) was conducted (NCT00766116). 194 GO was approved in 2000 as monotherapy for the treatment of relapsed AML but was later retired from the US market (in 2011) for its lack of efficacy and toxicity. The aforementioned clinical study has been started before GO market withdrawal, and the dose (6 mg/m 2 ) applied was the same used in therapy at that time.…”

mentioning

confidence: 99%

“…195 Therefore, additional studies are required to determine the optimal schedule and dose of GO in combination with azacytidine 1. 194 Histone methylation, as well as chromatin acetylation, are strongly implicated in androgen receptor (AR) protein functions and in mRNA splicing and transcription. 196,197 In particular, the balance between HDACs and HATs activities is very important for tuning transcriptional regulation of AR and its downstream targets.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Epigenetic polypharmacology: A new frontier for epi‐drug discovery

Tomaselli

Lucidi

Rotili

et al. 2019

Medicinal Research Reviews

View full text Add to dashboard Cite

Recently, despite the great success achieved by the so‐called “magic bullets” in the treatment of different diseases through a marked and specific interaction with the target of interest, the pharmacological research is moving toward the development of “molecular network active compounds,” embracing the related polypharmacology approach. This strategy was born to overcome the main limitations of the single target therapy leading to a superior therapeutic effect, a decrease of adverse reactions, and a reduction of potential mechanism(s) of drug resistance caused by robustness and redundancy of biological pathways. It has become clear that multifactorial diseases such as cancer, neurological, and inflammatory disorders, may require more complex therapeutic approaches hitting a certain biological system as a whole. Concerning epigenetics, the goal of the multi‐epi‐target approach consists in the development of small molecules able to simultaneously and (often) reversibly bind different specific epi‐targets. To date, two dual histone deacetylase/kinase inhibitors (CUDC‐101 and CUDC‐907) are in an advanced stage of clinical trials. In the last years, the growing interest in polypharmacology encouraged the publication of high‐quality reviews on combination therapy and hybrid molecules. Hence, to update the state‐of‐the‐art of these therapeutic approaches avoiding redundancy, herein we focused only on multiple medication therapies and multitargeting compounds exploiting epigenetic plus nonepigenetic drugs reported in the literature in 2018. In addition, all the multi‐epi‐target inhibitors known in literature so far, hitting two or more epigenetic targets, have been included.

show abstract

The promising role of antibody drug conjugate in cancer therapy: Combining targeting ability with cytotoxicity effectively

Guo

et al. 2021

Cancer Medicine

View full text Add to dashboard Cite

show abstract

A Phase I/II Trial of the Combination of Azacitidine and Gemtuzumab Ozogamicin for Treatment of Relapsed Acute Myeloid Leukemia

Cited by 33 publications

References 20 publications

Rapid Efficacy of Gemtuzumab Ozogamicin in Refractory AML Patients with Pulmonary and Kidney Failure

Rapid Efficacy of Gemtuzumab Ozogamicin in Refractory AML Patients with Pulmonary and Kidney Failure

Epigenetic polypharmacology: A new frontier for epi‐drug discovery

The promising role of antibody drug conjugate in cancer therapy: Combining targeting ability with cytotoxicity effectively

Contact Info

Product

Resources

About