FDA Approval Summary: Mylotarg for Treatment of Patients with Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia

Norsworthy, Kelly J.; Ko, Chia‐Wen; Lee, Jee Eun; Liu, Jiang; John, Christy S.; Przepiorka, Donna; Farrell, Ann T.; Pazdur, Richard

doi:10.1634/theoncologist.2017-0604

Cited by 172 publications

(141 citation statements)

References 30 publications

(39 reference statements)

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“…Furthermore, the study did not demonstrate an increased risk of sinusoidal obstructive syndrome (SOS) in the GO group as had been the case in early studies using higher doses of GO [2]. Based on the results of these studies, GO again earned Food and Drug Administration (FDA) approval in 2017 for the treatment of newly diagnosed CD33-positive AML in r/r adults and children ≥2 years of age [16]. This success story has led to the incorporation of GO into the backbone of the upcoming COG randomized controlled clinical trial, AAML1831, comparing CPX-351, a liposomal preparation of cytarabine and daunorubicin versus standard cytarabine and daunorubicin, expected to open for enrollment in the first quarter of 2020.…”

Section: Introductionmentioning

confidence: 92%

New and Emerging Targeted Therapies for Pediatric Acute Myeloid Leukemia (AML)

Chen

Glasser

2020

Children

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The relapse rate for children with acute myeloid leukemia (AML) remains high despite advancements in risk classification, multi-agent chemotherapy intensification, stem cell transplantation, and supportive care guidelines. Prognosis for this subgroup of children with relapsed/refractory AML remains poor. It is well known that the ceiling of chemotherapy intensification has been reached, limited by acute and chronic toxicity, necessitating alternative treatment approaches. In the last several years, our improved understanding of disease biology and critical molecular pathways in AML has yielded a variety of new drugs to target these specific pathways. This review provides a summary of antibody drug conjugates (ADCs), small molecule inhibitors, and tyrosine kinase inhibitors with an emphasis on those that are currently under clinical evaluation or soon to open in early phase trials for children with relapsed/refractory AML.

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Section: Introductionmentioning

confidence: 92%

New and Emerging Targeted Therapies for Pediatric Acute Myeloid Leukemia (AML)

Chen

Glasser

2020

Children

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“…Increase in Cmax was associated with a higher risk of hepatotoxicity, but no relationship between Cmax or AUC and complete remission (CR) rate was discovered. Therefore, responses to GO are not strictly dose dependent, particularly at high dose ranges [35].…”

Section: Gemtuzumab Ozogamicin (Go; Mylotarg)mentioning

confidence: 99%

“…Over the past decade, several investigational studies using fractionated dosing schedule of GO were completed and were able to improve the safety profiles without compromising the clinical efficacy [21,40,41]. Based on these promising results, GO gained re-approval from FDA in September 2017 as monotherapy or in combination with conventional chemotherapy for the treatment of newly-diagnosed CD33+ AML and relapsed or refractory (R/R) CD33+ AML in adults [35,42].…”

Section: Clinical Trials Of Go In Amlmentioning

confidence: 99%

Gemtuzumab ozogamicin and novel antibody-drug conjugates in clinical trials for acute myeloid leukemia

Liu

2019

Biomark Res

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Targeted agents are increasingly used for the therapy of acute myeloid leukemia (AML). Gemtuzumab ozogamicin (GO) is the first antibody-drug conjugate (ADC) approved for induction therapy of AML. When used in fractionated doses, GO combined with the conventional cytarabine/anthracycline-based induction chemotherapy significantly improves the outcome of previously untreated AML patients. Single-agent GO is effective and safe for AML patient ineligible for intensive chemotherapy. Multiple combination regimens incorporating GO have also been recommended as potential alternative options. In addition, several novel ADCs targeting CD33, CD123 and CLL-1 are currently undergoing preclinical or early clinical investigations. In this review, we summarized the efficacy and limitations of GO as well as novel ADCs for adult AML patients.

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“…Such a combination can potentially minimize dose‐limiting toxic side effects while maximizing desired therapeutic effects. Four FDA‐approved ADCs, Mylotarg (gemtuzumab ozogamicin; Norsworthy et al, ), Adcetris (brentuximab vedotin; Senter & Sievers, ) and Kadcyla (ado‐trastuzumab emtansine; Lewis Phillips et al, ) and Besponsa (inotuzumab ozogamicin; Lamb, ), have already reached the market and are followed closely by more than 80 ADCs now in clinical trials (Mullard, ).…”

Section: Antibody Conjugates and Fusionsmentioning

confidence: 99%

Antibody and antibody derivatives as cancer therapeutics

Arlotta

Owen

2019

WIREs Nanomed Nanobiotechnol

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Antibodies are an important class of therapeutic for treating a wide range of diseases. These versatile macromolecules can be engineered to target many different antigens and to utilize several mechanisms of action to produce a pharmacological effect. The most common antibody platform used for therapeutics is immunoglobulin G (IgG). Advances in protein-display and genetic engineering have enabled the construction and manipulation of IgG to enhance desired activity such as increasing antigen affinity, modulating pharmacokinetics, and enhancing effector functions.IgGs can also be altered to suppress undesired effects, such as immunogenicity. The main approaches to control IgG behavior include engineering the protein sequence and glycosylation of intact IgG; constructing IgG-based derivatives, including bispecific and multivalent binders; and fusing small-drug molecules or proteins to IgG-derived scaffolds. Often, a single modification applied to a given IgG can alter more than one property. The desired effects of an antibody therapeutic should be carefully tailored to the physiology and characteristics of each disease condition.

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FDA Approval Summary: Mylotarg for Treatment of Patients with Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia

Cited by 172 publications

References 30 publications

New and Emerging Targeted Therapies for Pediatric Acute Myeloid Leukemia (AML)

New and Emerging Targeted Therapies for Pediatric Acute Myeloid Leukemia (AML)

Gemtuzumab ozogamicin and novel antibody-drug conjugates in clinical trials for acute myeloid leukemia

Antibody and antibody derivatives as cancer therapeutics

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