関: gemtuzumab ozogamicin

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/04/15 00:53:30」(JST)

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Gemtuzumab ozogamicin (marketed by Wyeth as Mylotarg) is a drug-linked monoclonal antibody (an antibody-drug conjugate) that was used to treat acute myelogenous leukemia from 2000 to 2010. It was withdrawn from market in June 2010 when a clinical trial showed the drug increased patient death and added no benefit over conventional cancer therapies.

Gemtuzumab is a monoclonal antibody to CD33 linked to a cytotoxic agent from the class of calicheamicins. CD33 is expressed in most leukemic blast cells but also in normal hematopoietic cells, the intensity diminishing with maturation of stem cells. In the United States, it was approved under an accelerated-approval process by the FDA in 2000 for use in patients over the age of 60 with relapsed acute myelogenous leukemia (AML); or those who are not considered candidates for standard chemotherapy.^[1]

Within the first year after approval, the FDA required a black box warning be added to Gemtuzumab packaging. The drug was noted to increase the risk of veno-occlusive disease in the absence of bone marrow transplantation.^[2] Later the onset of VOD was shown to occur at increased frequency in Gemtuzumab patients even following bone marrow transplantation.^[3] The drug was discussed in a 2008 JAMA article, which criticized the inadequacy of postmarketing surveillance of biologic agents.^[4]

Common side effects of administration included shivering, fever, nausea and vomiting. Serious side effects included severe myelosuppression (suppressed activity of bone marrow, which is involved in formation of various blood cells [found in 98% of patients]), disorder of the respiratory system, tumor lysis syndrome, Type III hypersensitivity, venous occlusion, and death.

Withdrawal from market

A randomized phase 3 comparative controlled trial (SWOG S0106) was initiated in 2004 by Wyeth in accordance with the FDA accelerated-approval process. The study was stopped prior to completion due to worrisome outcomes. Among the patients evaluated, fatal toxicity rate was significantly higher in the gemtuzumab combination therapy group vs the standard therapy group. Mortality was 5.7% with gemtuzumab and 1.4% without the agent (16/283 = 5.7% vs 4/281 = 1.4%; P = .01).^[5]

In June 2010, Pfizer withdrew Mylotarg from the market at the request of the US FDA.^[6]^[7] However, some other regulatory authorities did not agree with the FDA decision, with Japan's Pharmaceuticals and Medical Devices Agency stating in 2011 that the "risk-benefit balance of gemtuzumab ozogamicin has not changed from its state at the time of approval".^[8]

References

^ Bross PF, Beitz J, Chewn G, Chen XH, Duffy E, Kieffer L, Roy S, Sridhara R, Rahman A, Williams G, Pazdur R (2001). "Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia.". Clin Cancer Res 7 (6): 1490–6. PMID 11410481.
^ Giles FJ, Kantarjian HM, Kornblau SM, Thomas DA, Garcia-Manero G, Waddelow TA, David CL, Phan AT, Colburn DE, Rashid A, Estey EH (2001). "Mylotarg (gemtuzumab ozogamicin) therapy is associated with hepatic venoocclusive disease in patients who have not received stem cell transplantation.". Cancer 92 (2): 406–13. doi:10.1002/1097-0142(20010715)92:2<406::AID-CNCR1336>3.0.CO;2-U. PMID 11466696.
^ Wadleigh M, Richardson PG, Zahrieh D, Lee SJ, Cutler C, Ho V, Alyea EP, Antin JH, Stone RM, Soiffer RJ, DeAngelo DJ (2003). "Prior gemtuzumab ozogamicin exposure significantly increases the risk of veno-occlusive disease in patients who undergo myeloablative allogeneic stem cell transplantation.". Blood 102 (5): 1578–82. doi:10.1182/blood-2003-01-0255. PMID 12738663.
^ The Research on Adverse Drug Events and Reports (RADAR) Project, JAMA
^ [1], Medscape
^ Mylotarg (gemtuzumab ozogamicin): Market Withdrawal, US FDA
^ Pfizer pulls leukemia drug from U.S. market, Reuters
^ Pharmaceuticals and Medical Devices Safety Information, No. 277, February 2011 (PDF) (Technical report). Pharmaceuticals and Medical Devices Agency of Japan. 2011.

UpToDate Contents

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1. 再発性または難治性の急性骨髄性白血病の治療 treatment of relapsed or refractory acute myeloid leukemia
2. 高齢者における急性骨髄性白血病の治療 treatment of acute myeloid leukemia in older adults
3. 再発性および難治性の急性前骨髄球性白血病の治療 treatment of relapsed or refractory acute promyelocytic leukemia in adults
4. Determining eligibility for allogeneic hematopoietic cell transplantation
5. 若年成人における急性骨髄性白血病に対する導入療法 induction therapy for acute myeloid leukemia in younger adults

English Journal

Gemtuzumab Ozogamicin Versus Best Supportive Care in Older Patients With Newly Diagnosed Acute Myeloid Leukemia Unsuitable for Intensive Chemotherapy: Results of the Randomized Phase III EORTC-GIMEMA AML-19 Trial.

Amadori S1, Suciu S2, Selleslag D2, Aversa F2, Gaidano G2, Musso M2, Annino L2, Venditti A2, Voso MT2, Mazzone C2, Magro D2, De Fabritiis P2, Muus P2, Alimena G2, Mancini M2, Hagemeijer A2, Paoloni F2, Vignetti M2, Fazi P2, Meert L2, Ramadan SM2, Willemze R2, de Witte T2, Baron F2.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology.J Clin Oncol.2016 Mar 20;34(9):972-9. doi: 10.1200/JCO.2015.64.0060. Epub 2016 Jan 25.
PURPOSE: To compare single-agent gemtuzumab ozogamicin (GO) with best supportive care (BSC) including hydroxyurea as first-line therapy in older patients with acute myeloid leukemia unsuitable for intensive chemotherapy.PATIENTS AND METHODS: In this trial, patients at least 61 years old were central
PMID 26811524

The addition of gemtuzumab ozogamicin to chemotherapy in adult patients with acute myeloid leukemia.

Kell J1.
Expert review of anticancer therapy.Expert Rev Anticancer Ther.2016 Mar 4. [Epub ahead of print]
The treatment of acute myeloid leukaemia has remained largely unchanged for the last 30 years since the advent of combination chemotherapy with cytarabine arabinoside and daunorubicin with remission rates around 70% but with long term survival still only around 40% in young adults. Doses of chemothe
PMID 26942450

Optimal treatment strategies for high-risk acute promyelocytic leukemia.

Norsworthy KJ1, Altman JK.
Current opinion in hematology.Curr Opin Hematol.2016 Mar;23(2):127-36. doi: 10.1097/MOH.0000000000000215.
PURPOSE OF REVIEW: Despite major advances in the treatment of acute promyelocytic leukemia (APL), high-risk APL still poses unique challenges. The purpose of this review is to outline current evidence for evaluation and management of high-risk APL and discuss areas of ongoing and future investigatio
PMID 26825698

Japanese Journal

再発・難治APLに対するGO monotherapy

竹下明裕
血液内科 65(3), 394-400, 2012-09-00
NAID 40019458213

注目の領域米国での医薬品迅速承認制度の現状と課題 : midodrine,gemtuzumab ozogamicin,bevacizumabを例に

太田有子,天沼喜美子,青木良子 [他]
医学のあゆみ 242(8), 612-620, 2012-08-25
NAID 40019381359

急性骨髄性白血病(AML)に対するgemtuzumab ozogamicinの臨床的有用性に関する最近の考え方

薄井紀子
血液内科 65(2), 245-253, 2012-08-00
NAID 40019425597

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★リンクテーブル★

リンク元	「mab」「ゲムツズマブ」

「mab」

Gemtuzumab ozogamicin
Monoclonal antibody
Type	Whole antibody
Source	Humanized (from mouse)
Target	CD33
Clinical data
Trade names	Mylotarg
AHFS/Drugs.com	monograph
MedlinePlus	a607075
Pregnancy; category	D;
Routes of; administration	Intravenous
Legal status
Legal status	US: ℞-only;
Identifiers
CAS Number	220578-59-6
ATC code	L01XC05 (WHO)
DrugBank	DB00056
ChemSpider	none
KEGG	D03259
ChEMBL	CHEMBL1201506
Chemical data
Molar mass	151–153 g/mol
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