Difference between revisions of "Gemtuzumab ozogamicin (Mylotarg)"

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m (Text replacement - "please refer to your preferred pharmacopeias such as [http://www.thomsonhc.com/home/dispatch Micromedex], [https://online.lexi.com/lco/action/login UpToDate Lexidrug], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information" to "please refer to your preferred pharmacopeias or the prescribing information")
 
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==General information==
 
==General information==
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Class/mechanism: Antibody-cytotoxic agent conjugate. Gemtuzumab ozogamicin is comprised of a recombinant humanized IgG4 kappa antibody against CD33--an adhesion protein expressed on the surface of leukemic blasts and immature normal cells of myelomonocytic lineage, but not on normal hematopoietic stem cells--conjugated with a cytotoxic agent, calicheamicin. The antibody-cytotoxic agent is internalized after binding, and the calicheamicin derivative binds to DNA in the minor groove, causing DNA double strand breaks and cell death.<ref name="insert">[http://labeling.pfizer.com/showlabeling.aspx?id=119 Gemtuzumab ozogamicin (Mylotarg) package insert]</ref><ref>[http://hemonc.org/docs/packageinsert/gemtuzumabozogamicin.pdf Gemtuzumab ozogamicin (Mylotarg) package insert (locally hosted backup)]</ref>
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Class/mechanism: Antibody-cytotoxic agent conjugate. Gemtuzumab ozogamicin is comprised of a recombinant humanized IgG4 kappa antibody against CD33--an adhesion protein expressed on the surface of leukemic blasts and immature normal cells of myelomonocytic lineage, but not on normal hematopoietic stem cells--conjugated with a cytotoxic agent, calicheamicin. The antibody-cytotoxic agent is internalized after binding, and the calicheamicin derivative binds to DNA in the minor groove, causing DNA double strand breaks and cell death.<ref name="insert">[http://labeling.pfizer.com/showlabeling.aspx?id=119 Gemtuzumab ozogamicin (Mylotarg) package insert]</ref><ref>[https://hemonc.org/docs/packageinsert/gemtuzumabozogamicin.pdf Gemtuzumab ozogamicin (Mylotarg) package insert (locally hosted backup)]</ref>
 
<br>Route: IV
 
<br>Route: IV
 
<br>Extravasation: no information
 
<br>Extravasation: no information
  
−
For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as [http://www.thomsonhc.com/home/dispatch Micromedex], [http://online.lexi.com/ Lexicomp], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information.<ref name="insert"></ref>
+
For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias or the prescribing information.<ref name="insert"></ref>
  
 +
==Diseases for which it is established==
 +
*[[Acute myeloid leukemia]]
 
==Diseases for which it is used==
 
==Diseases for which it is used==
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''Gemtuzumab ozogamicin is currently withdrawn from the market so these references are for historical purposes, only.''
 
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*[[Acute myeloid leukemia]]
 
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===References===
 
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# Sievers EL, Larson RA, Stadtmauer EA, Estey E, Löwenberg B, Dombret H, Karanes C, Theobald M, Bennett JM, Sherman ML, Berger MS, Eten CB, Loken MR, van Dongen JJ, Bernstein ID, Appelbaum FR; Mylotarg Study Group. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J Clin Oncol. 2001 Jul 1;19(13):3244-54. [http://jco.ascopubs.org/content/19/13/3244.long link to original article]  [http://www.ncbi.nlm.nih.gov/pubmed/11432892 PubMed]
 
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# Petersdorf SH, Kopecky KJ, Slovak M, Willman C, Nevill T, Brandwein J, Larson RA, Erba HP, Stiff PJ, Stuart RK, Walter RB, Tallman MS, Stenke L, Appelbaum FR. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood. 2013 Jun 13;121(24):4854-60. Epub 2013 Apr 16. [http://bloodjournal.hematologylibrary.org/content/121/24/4854.long link to original article]  [http://www.ncbi.nlm.nih.gov/pubmed/23591789 PubMed]
 
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# '''Abstract:''' '''Meta-analysis:''' Stephen Petersdorf, Elihu H. Estey, Megan Othus, Frederick R. Appelbaum, Sylvie Castaigne, Herve Dombret, Sylvie Chevret, Jacques Delaunay, Norbert Ifrah, Jean-Yves Cahn, Christian Recher, Alan K Burnett. The Addition Of Gemtuzumab Ozogamicin (GO) To Induction Chemotherapy Reduces Relapse and Improves Survival In Patients Without Adverse Risk Karyotype: Results Of An Individual Patient Meta-Analysis Of The Five Randomised Trials. Blood Nov 2013,122(21)356 [http://bloodjournal.hematologylibrary.org/content/122/21/356 link to original abstract]
 
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==Azacitidine, Gemtuzumab & Vorinostat==
 
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===Regimen, Walter et al. 2013===
 
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<span
 
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style="background:#EEEE00;
 
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padding:3px 6px 3px 6px;
 
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border-color:black;
 
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border-width:2px;
 
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border-style:solid;">Phase I/II</span>
 
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''This is the MTD used in the phase II portion, which was tested on 43 patients.''
 
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*[[Azacitidine (Vidaza)]] 75 mg/m2 SC or IV once per day on days 1 to 7
 
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*[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m2 IV once on days 4 & 8
 
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*[[Vorinostat (Zolinza)]] 400 mg PO once per day on days 1 to 9
 
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'''Up to 6 cycles based on response; cycle length not specified beyond 2nd cycle'''
 
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===References===
 
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# Walter RB, Medeiros BC, Gardner KM, Orlowski KF, Gallegos L, Scott BL, Hendrie PC, Estey EH. Gemtuzumab ozogamicin in combination with vorinostat and azacitidine in older patients with relapsed or refractory acute myeloid leukemia: a phase 1/2 study. Haematologica. 2013 Oct 18. [Epub ahead of print] [http://www.haematologica.org/content/99/1/54.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24142996 PubMed]
 
−
 
 
*[[Acute promyelocytic leukemia]]
 
*[[Acute promyelocytic leukemia]]
  
 
==Patient drug information==
 
==Patient drug information==
 +
*[http://labeling.pfizer.com/showlabeling.aspx?id=119 Gemtuzumab ozogamicin (Mylotarg) package insert]<ref name="insert"></ref>
 
*[http://www.chemocare.com/bio/gemtuzumab_ozogamicin.asp Gemtuzumab ozogamicin (Mylotarg) patient drug information (Chemocare)]<ref>[http://www.chemocare.com/bio/gemtuzumab_ozogamicin.asp Gemtuzumab ozogamicin (Mylotarg) patient drug information (Chemocare)]</ref>
 
*[http://www.chemocare.com/bio/gemtuzumab_ozogamicin.asp Gemtuzumab ozogamicin (Mylotarg) patient drug information (Chemocare)]<ref>[http://www.chemocare.com/bio/gemtuzumab_ozogamicin.asp Gemtuzumab ozogamicin (Mylotarg) patient drug information (Chemocare)]</ref>
  
 
==History of changes in FDA indication==
 
==History of changes in FDA indication==
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*5/17/2000: Granted FDA accelerated approval for the treatment of patients with [[Acute myeloid leukemia | CD33 positive acute myeloid leukemia]] in first relapse who are 60 years of age or older and who are not considered candidates for cytotoxic chemotherapy.
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*2000-05-17: Granted accelerated approval for the treatment of patients with [[Biomarkers#CD33|CD33]] [[Biomarkers#Expression|positive]] [[Acute myeloid leukemia | acute myeloid leukemia]] in first relapse who are 60 years of age or older and who are not considered candidates for cytotoxic chemotherapy. ''(Based on GO study 1, GO study 2, and GO study 3)''
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*10/15/2010: '''Withdrawn from US market'''<ref>[http://www.pfizer.com/files/products/mylotarg_hcp_letter.pdf Pfizer letter to healthcare providers (6/21/2010)]</ref>, but there are ongoing investigations regarding reintroduction into the US.
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**2011-11-28: Accelerated approval for [[acute myeloid leukemia]] withdrawn. ''(Based on SWOG S0106)''
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*2017-09-01: New approval for the treatment of newly-diagnosed [[Biomarkers#CD33|CD33]]-[[Biomarkers#Expression|positive]] [[Acute myeloid leukemia |acute myeloid leukemia (AML)]] in adults. Gemtuzumab ozogamicin may be used in combination with daunorubicin and cytarabine for adults with newly-diagnosed AML. ''(Based on ALFA-0701 and EORTC/GIMEMA AML-19)''
 +
*2017-09-01: New approval for treatment of relapsed or refractory [[Biomarkers#CD33|CD33]]-[[Biomarkers#Expression|positive]] [[Acute myeloid leukemia |AML]] in adults and in pediatric patients 2 years and older. ''(Based on MyloFrance-1)''
 +
*2020-06-16: Approved for newly-diagnosed [[Biomarkers#CD33|CD33]]-[[Biomarkers#Expression|positive]] [[Acute myeloid leukemia|acute myeloid leukemia (AML)]] to include pediatric patients 1 month and older. ''(Approval expanded to pediatric patients 1 month and older; based on COG AAML0531)''
 +
 
 +
==History of changes in EMA indication==
 +
*2018-04-19: Marketing authorisation (unclear if this is initial or re-authorisation)
 +
*Uncertain date: Mylotarg is indicated for combination therapy with daunorubicin (DNR) and cytarabine (AraC) for the treatment of patients age 15 years and above with previously untreated, de novo CD33-positive [[Acute myeloid leukemia|acute myeloid leukaemia (AML)]], except acute promyelocytic leukaemia (APL). ''(Based on ALFA-0701)''
 +
 
 +
==History of changes in Health Canada indication==
 +
*2019-11-28: Initial notice of compliance
 +
==History of changes in PMDA indication==
 +
*2005-07-25: Initial approval for the treatment of relapsing or intractable CD33 positive [[acute myeloid leukemia]].
 +
==Also known as==
 +
*'''Brand name:''' Mylotarg
  
 
==References==
 
==References==
 
<references/>
 
<references/>
  
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[[Category:Drug index]]
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[[Category:Drugs]]
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[[Category:Chemotherapy]]
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[[Category:Intravenous medications]]
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[[Category:Antibody-drug conjugates]]
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[[Category:Protein expression-specific medications]]
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 +
[[Category:Anti-CD33 antibody-drug conjugates]]
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[[Category:Enediyne antibiotic]]
 +
 
 
[[Category:Acute myeloid leukemia medications]]
 
[[Category:Acute myeloid leukemia medications]]
 
[[Category:Acute promyelocytic leukemia medications]]
 
[[Category:Acute promyelocytic leukemia medications]]
  
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[[Category:Discontinued]]
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[[Category:FDA approved in 2000]]
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[[Category:Drugs FDA approved in 2000]]
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[[Category:FDA withdrawn in 2011]]
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[[Category:FDA approved in 2017]]
 +
[[Category:EMA approved in 2018]]
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[[Category:Health Canada approved in 2019]]
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[[Category:PMDA approved in 2005]]

Latest revision as of 01:06, 29 June 2024

General information

Class/mechanism: Antibody-cytotoxic agent conjugate. Gemtuzumab ozogamicin is comprised of a recombinant humanized IgG4 kappa antibody against CD33--an adhesion protein expressed on the surface of leukemic blasts and immature normal cells of myelomonocytic lineage, but not on normal hematopoietic stem cells--conjugated with a cytotoxic agent, calicheamicin. The antibody-cytotoxic agent is internalized after binding, and the calicheamicin derivative binds to DNA in the minor groove, causing DNA double strand breaks and cell death.[1][2]
Route: IV
Extravasation: no information

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias or the prescribing information.[1]

Diseases for which it is established

Diseases for which it is used

Patient drug information

History of changes in FDA indication

  • 2000-05-17: Granted accelerated approval for the treatment of patients with CD33 positive acute myeloid leukemia in first relapse who are 60 years of age or older and who are not considered candidates for cytotoxic chemotherapy. (Based on GO study 1, GO study 2, and GO study 3)
  • 2017-09-01: New approval for the treatment of newly-diagnosed CD33-positive acute myeloid leukemia (AML) in adults. Gemtuzumab ozogamicin may be used in combination with daunorubicin and cytarabine for adults with newly-diagnosed AML. (Based on ALFA-0701 and EORTC/GIMEMA AML-19)
  • 2017-09-01: New approval for treatment of relapsed or refractory CD33-positive AML in adults and in pediatric patients 2 years and older. (Based on MyloFrance-1)
  • 2020-06-16: Approved for newly-diagnosed CD33-positive acute myeloid leukemia (AML) to include pediatric patients 1 month and older. (Approval expanded to pediatric patients 1 month and older; based on COG AAML0531)

History of changes in EMA indication

  • 2018-04-19: Marketing authorisation (unclear if this is initial or re-authorisation)
  • Uncertain date: Mylotarg is indicated for combination therapy with daunorubicin (DNR) and cytarabine (AraC) for the treatment of patients age 15 years and above with previously untreated, de novo CD33-positive acute myeloid leukaemia (AML), except acute promyelocytic leukaemia (APL). (Based on ALFA-0701)

History of changes in Health Canada indication

  • 2019-11-28: Initial notice of compliance

History of changes in PMDA indication

  • 2005-07-25: Initial approval for the treatment of relapsing or intractable CD33 positive acute myeloid leukemia.

Also known as

  • Brand name: Mylotarg

References

  1. ↑ 1.0 1.1 1.2 Gemtuzumab ozogamicin (Mylotarg) package insert
  2. ↑ Gemtuzumab ozogamicin (Mylotarg) package insert (locally hosted backup)
  3. ↑ Gemtuzumab ozogamicin (Mylotarg) patient drug information (Chemocare)
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