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Gemtuzumab ozogamicin

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Gemtuzumab ozogamicin
Monoclonal antibody
TypeWhole antibody
SourceHumanized (from mouse)
Clinical data
Trade namesMylotarg
License data
Routes of
ATC code
Legal status
Legal status
CAS Number
  • none
Chemical and physical data
Molar mass151500 g·mol−1
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Gemtuzumab ozogamicin, sold under the brand name Mylotarg, is an antibody-drug conjugate (a drug-linked monoclonal antibody) that is used to treat acute myeloid leukemia.[6][8][9]

The most common side effects include infection, febrile neutropenia, decreased appetite, hyperglycemia, mucositis, hypoxia, hemorrhage, increased transaminase, diarrhea, nausea, and hypotension.[10] However, the addition of gemtuzumab ozogamicin to standard chemotherapy regimens does not increase infection rates. [11]

Medical uses[edit]

In the United States, gemtuzumab ozogamicin is indicated for newly diagnosed CD33-positive acute myeloid leukemia (AML) for adults and children one month and older and for the treatment of relapsed or refractory CD33-positive AML in adults and children two years and older.[6][10]


Mechanism of action of gemtuzumab ozogamicin

Gemtuzumab is a monoclonal antibody to CD33 linked to a cytotoxic agent from the class of calicheamicins (ozogamicin).[6] CD33 is expressed in most leukemic blast cells but also in normal hematopoietic cells, the intensity diminishing with maturation of stem cells.[6]


Gemtuzumab ozogamicin was created in a collaboration between Celltech and Wyeth that began in 1991.[12][13] The same collaboration later produced inotuzumab ozogamicin.[14] Celltech was acquired by UCB in 2004[15] and Wyeth was acquired by Pfizer in 2009.[16]

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.[17] The accelerated approval was based on the surrogate endpoint of response rate.[18] It was the first antibody-drug conjugate to be approved.[19]

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.[20] Later the onset of VOD was shown to occur at increased frequency in gemtuzumab patients even following bone marrow transplantation.[21] The drug was discussed in a 2008 JAMA article, which criticized the inadequacy of postmarketing surveillance of biologic agents.[22]

A randomized Phase III comparative controlled trial (SWOG S0106) was initiated in 2004, by Wyeth in accordance with the FDA accelerated-approval process. The study was stopped on August 20, 2009, prior to completion due to worrisome outcomes.[23] Among the patients evaluated for early toxicity, 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).[18]

In June 2010, Pfizer withdrew Mylotarg from the market at the request of the US FDA.[24][25] 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".[26]

In 2017, Pfizer reapplied for US and EU approval, based on a meta-analysis of prior trials and results of the ALFA-0701 clinical trial, an open-label Phase III trial in 280 older people with AML.[19] In September 2017, gemtuzumab ozogamicin was approved again for use in the United States[8][27] and in the European Union.[7]


  1. ^ a b "Mylotarg Australian prescription medicine decision summary". Therapeutic Goods Administration (TGA). 17 April 2020. Retrieved 17 August 2020.
  2. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  3. ^ AusPAR: Gemtuzumab ozogamicin. Therapeutic Goods Administration (TGA) (Report). October 2020.
  4. ^ "Summary Basis of Decision (SBD) for Mylotarg". Health Canada. 23 October 2014. Retrieved 29 May 2022.
  5. ^ "Mylotarg 5mg powder for concentrate for solution for infusion - Summary of Product Characteristics (SmPC)". (emc). 29 October 2019. Retrieved 17 August 2020.
  6. ^ a b c d e "Mylotarg- gemtuzumab ozogamicin injection, powder, lyophilized, for solution". DailyMed. 29 June 2020. Retrieved 17 August 2020.
  7. ^ a b "Mylotarg EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 28 February 2020.
  8. ^ a b "FDA approves Mylotarg for treatment of acute myeloid leukemia". U.S. Food and Drug Administration (FDA) (Press release). 1 September 2017. Retrieved 16 August 2020.
  9. ^ "FDA Approves Gemtuzumab Ozogamicin for CD33-positive AML". U.S. Food and Drug Administration (FDA) (Press release). 1 September 2017. Retrieved 6 September 2017. Public Domain This article incorporates text from this source, which is in the public domain.
  10. ^ a b "FDA approves gemtuzumab ozogamicin for CD33-positive AML in pediatric patients". U.S. Food and Drug Administration (FDA) (Press release). 16 June 2020. Retrieved 16 June 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  11. ^ Kyriakidis I, Mantadakis E, Stiakaki E, Groll AH, Tragiannidis A (October 2022). "Infectious Complications of Targeted Therapies in Children with Leukemias and Lymphomas". Cancers. 14 (20): 5022. doi:10.3390/cancers14205022. PMC 9599435. PMID 36291806.
  12. ^ "Mylotarg". Informa Biomedtracker. Archived from the original on 19 August 2017. Retrieved 19 August 2017.
  13. ^ Niculescu-Duvaz I (December 2000). "Technology evaluation: gemtuzumab ozogamicin, Celltech Group". Current Opinion in Molecular Therapeutics. 2 (6): 691–696. PMID 11249747.
  14. ^ Damle NK, Frost P (August 2003). "Antibody-targeted chemotherapy with immunoconjugates of calicheamicin". Current Opinion in Pharmacology. 3 (4): 386–390. doi:10.1016/S1471-4892(03)00083-3. PMID 12901947.
  15. ^ "Celltech sold to Belgian firm in £1.5bn deal". The Guardian. 18 May 2004.
  16. ^ Sorkin AR, Wilson D (25 January 2009). "Pfizer Agrees to Pay $68 Billion for Rival Drug Maker Wyeth". The New York Times.
  17. ^ Bross PF, Beitz J, Chen G, Chen XH, Duffy E, Kieffer L, et al. (June 2001). "Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia". Clinical Cancer Research. 7 (6): 1490–1496. PMID 11410481.
  18. ^ a b Gemtuzumab Voluntarily Withdrawn From US Market. June 2010
  19. ^ a b Stanton D (1 February 2017). "Pfizer resubmits US and EU application for withdrawn ADC Mylotarg". BioPharma Reporter.
  20. ^ Giles FJ, Kantarjian HM, Kornblau SM, Thomas DA, Garcia-Manero G, Waddelow TA, et al. (July 2001). "Mylotarg (gemtuzumab ozogamicin) therapy is associated with hepatic venoocclusive disease in patients who have not received stem cell transplantation". Cancer. 92 (2): 406–413. doi:10.1002/1097-0142(20010715)92:2<406::AID-CNCR1336>3.0.CO;2-U. PMID 11466696. S2CID 28510415.
  21. ^ Wadleigh M, Richardson PG, Zahrieh D, Lee SJ, Cutler C, Ho V, et al. (September 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): 1578–1582. doi:10.1182/blood-2003-01-0255. PMID 12738663.
  22. ^ The Research on Adverse Drug Events and Reports (RADAR) Project, JAMA
  23. ^ Petersdorf SH, Kopecky KJ, Slovak M, Willman C, Nevill T, Brandwein J, et al. (June 2013). "A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia". Blood. 121 (24): 4854–4860. doi:10.1182/blood-2013-01-466706. PMC 3682338. PMID 23591789.
  24. ^ Mylotarg (gemtuzumab ozogamicin): Market Withdrawal, US FDA
  25. ^ Pfizer pulls leukemia drug from U.S. market, Reuters
  26. ^ Pharmaceuticals and Medical Devices Safety Information, No. 277, February 2011 (PDF) (Technical report). Pharmaceuticals and Medical Devices Agency of Japan. 2011. Archived from the original (PDF) on 20 January 2013. Retrieved 6 July 2013.
  27. ^ "Drug Approval Package: Mylotarg (gemtuzumab ozogamicin)". U.S. Food and Drug Administration (FDA). 7 June 2018. Retrieved 16 August 2020.

External links[edit]

  • Clinical trial number NCT00372593 for "Combination Chemotherapy With or Without Gemtuzumab in Treating Young Patients With Newly Diagnosed Acute Myeloid Leukemia" at ClinicalTrials.gov