Difference between revisions of "Gemtuzumab ozogamicin (Mylotarg)"

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

Acute myeloid leukemia

Diseases for which it is used

Acute promyelocytic leukemia

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)
- 2011-11-28: Accelerated approval for acute myeloid leukemia withdrawn. (Based on SWOG S0106)
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

[insert-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)

[1]

[2]

[3]

@@ Line 1: / Line 1: @@
 ==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.<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>
+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>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==
-''Gemtuzumab ozogamicin is currently withdrawn from the market so these references are for historical purposes, only. If the drug is re-introduced these will be moved back to active page(s).''
-*[[Acute myeloid leukemia]]
-===References===
-# 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]  [https://www.ncbi.nlm.nih.gov/pubmed/11432892 PubMed]
-# Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association.. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 2012 Apr 21;379(9825):1508-16. [https://www.ncbi.nlm.nih.gov/pubmed/22482940 PubMed]
-# 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]  [https://www.ncbi.nlm.nih.gov/pubmed/23591789 PubMed]
-# '''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]
-<!-- Presented in part at the 56th Annual Meeting of the American Society of Hematology, San Francisco, CA, December 6-9, 2014. -->
-# Amadori S, Suciu S, Selleslag D, Aversa F, Gaidano G, Musso M, Annino L, Venditti A, Voso MT, Mazzone C, Magro D, De Fabritiis P, Muus P, Alimena G, Mancini M, Hagemeijer A, Paoloni F, Vignetti M, Fazi P, Meert L, Ramadan SM, Willemze R, de Witte T, Baron F. 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. J Clin Oncol. 2016 Mar 20;34(9):972-9. Epub 2016 Jan 25. [http://jco.ascopubs.org/content/34/9/972.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26811524 PubMed]
-# '''GO-A-HAM:''' Hütter-Krönke ML, Benner A, Döhner K, Krauter J, Weber D, Moessner M, Köhne CH, Horst HA, Schmidt-Wolf IG, Rummel M, Götze K, Koller E, Petzer AL, Salwender H, Fiedler W, Kirchen H, Haase D, Kremers S, Theobald M, Matzdorff AC, Ganser A,  Döhner H, Schlenk RF. Salvage therapy with high-dose cytarabine and mitoxantrone in combination with all-trans retinoic acid and gemtuzumab ozogamicin in acute myeloid leukemia refractory to first induction therapy. Haematologica. 2016 Apr 1. [Epub ahead of print] [http://www.haematologica.org/content/101/7/839 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27036160 PubMed]
-==Azacitidine & Gemtuzumab ozogamicin {{#subobject:6f77be|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:188f5c|Variant=1}}===
-{| border="1" style="text-align:center;" !align="left"
-|'''Study'''
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|-
-|[http://informahealthcare.com/doi/full/10.1080/10428190802451254 Nand et al. 2008]
-|style="background-color:#EEEE00"|Phase II
-|-
-|[http://bloodjournal.hematologylibrary.org/content/122/20/3432.full Nand et al. 2013]
-|style="background-color:#EEEE00"|Phase II
-|-
-|}
-''Patients with WBC > 10k at presentation were pre-treated with Hydrea. Leukapheresis was recommended for patients with WBC > 100k. Nand et al. 2008 did not describe the maintenance portion of the regimen, and used only SC azacitidine.''
-====Pre-treatment phase====
-*[[Hydroxyurea (Hydrea)]] 1500 mg PO twice per day or "in higher doses if necessary"
-'''Once WBC is less than 10k, stop Hydrea and proceed:'''
-====Induction====
-*[[Azacitidine (Vidaza)]] 75 mg/m2 SC or IV once per day on days 1 to 7
-*[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m2 IV once on day 8
-Supportive medications:
-*"Appropriate premedications" which were not specified, for [[Gemtuzumab ozogamicin (Mylotarg)]]
-''If D14 bone marrow with ≥5% blasts, a second induction cycle identical to the first was administered. Patients achieving CR or CRi were to receive [[Acute_myeloid_leukemia#Azacitidine_.26_Gemtuzumab_ozogamicin_2|azacitidine and gemtuzumab ozogamicin consolidation]] within 60 days.''
-===References===
-# Nand S, Godwin J, Smith S, Barton K, Michaelis L, Alkan S, Veerappan R, Rychlik K, Germano E, Stiff P. Hydroxyurea, azacitidine and gemtuzumab ozogamicin therapy in patients with previously untreated non-M3 acute myeloid leukemia and high-risk myelodysplastic syndromes in the elderly: results from a pilot trial. Leuk Lymphoma. 2008 Nov;49(11):2141-7. [http://informahealthcare.com/doi/full/10.1080/10428190802451254 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19021057 PubMed]
-<!-- Presented in part at the American Society of Clinical Oncology annual meeting (Chicago, IL, June 1-5, 2012) and at the American Society of Hematology annual meeting (Atlanta, GA, December 8-11, 2012). -->
-# Nand S, Othus M, Godwin JE, Willman CL, Norwood TH, Howard DS, Coutre SE, Erba HP, Appelbaum FR. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood. 2013 Nov 14;122(20):3432-9. Epub 2013 Oct 3. [http://bloodjournal.hematologylibrary.org/content/122/20/3432.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24092933 PubMed]
-==Azacitidine & Gemtuzumab ozogamicin {{#subobject:e5ff95|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:eb3f69|Variant=1}}===
-{| border="1" style="text-align:center;" !align="left"
-|'''Study'''
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|-
-|[http://bloodjournal.hematologylibrary.org/content/122/20/3432.full Nand et al. 2013]
-|style="background-color:#EEEE00"|Phase II
-|-
-|}
-''Treatment preceded by [[Acute_myeloid_leukemia#Azacitidine_.26_Gemtuzumab_ozogamicin|azacitidine and gemtuzumab ozogamicin]] induction.''
-*[[Azacitidine (Vidaza)]] 75 mg/m2 SC or IV once per day on days 1 to 7
-*[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m2 IV once on day 8
-Supportive medications:
-*"Appropriate premedications" which were not specified, for [[Gemtuzumab ozogamicin (Mylotarg)]]
-*Growth factors per physician discretion
-'''1 cycle'''
-''Patients were to start [[Acute_myeloid_leukemia#Azacitidine_.28Vidaza.29_2|azacitidine maintenance]] within 42 days of completion of consolidation.''
-===References===
-<!-- Presented in part at the American Society of Clinical Oncology annual meeting (Chicago, IL, June 1-5, 2012) and at the American Society of Hematology annual meeting (Atlanta, GA, December 8-11, 2012). -->
-# Nand S, Othus M, Godwin JE, Willman CL, Norwood TH, Howard DS, Coutre SE, Erba HP, Appelbaum FR. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood. 2013 Nov 14;122(20):3432-9. Epub 2013 Oct 3. [http://bloodjournal.hematologylibrary.org/content/122/20/3432.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24092933 PubMed]
-==Azacitidine, Gemtuzumab & Vorinostat==
-===Regimen===
-{| border="1" style="text-align:center;" !align="left"
-|'''Study'''
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|-
-|[http://www.haematologica.org/content/99/1/54.full Walter et al. 2013]
-|style="background-color:#EEEE00"|Phase I/II
-|-
-|}
-''This is the MTD used in the phase II portion, which was tested on 43 patients.''
-*[[Azacitidine (Vidaza)]] 75 mg/m2 SC or IV once per day on days 1 to 7
-*[[Gemtuzumab ozogamicin (Mylotarg)]] 3 mg/m2 IV once on days 4 & 8
-*[[Vorinostat (Zolinza)]] 400 mg PO once per day on days 1 to 9
-'''Up to 6 cycles based on response; cycle length not specified beyond 2nd cycle'''
-===References===
-# 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''' [https://www.ncbi.nlm.nih.gov/pubmed/24142996 PubMed]
 *[[Acute promyelocytic leukemia]]
 ==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>
 ==History of changes in FDA indication==
-*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.
+*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)''
-*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.
+**2011-11-28: Accelerated approval for [[acute myeloid leukemia]] withdrawn. ''(Based on SWOG S0106)''
+*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/>
-[[Category:Drug index]]
+[[Category:Drugs]]
-[[Category:Chemotherapy]]
 [[Category:Intravenous medications]]
+[[Category:Protein expression-specific medications]]
-[[Category:Antibody medications]]
+[[Category:Anti-CD33 antibody-drug conjugates]]
-[[Category:Antibody-drug conjugates]]
-[[Category:Anti-CD33 antibodies]]
 [[Category:Enediyne antibiotic]]
@@ Line 137: / Line 46: @@
 [[Category:Acute promyelocytic leukemia medications]]
-[[Category:Discontinued]]
+[[Category:FDA approved in 2000]]
-[[Category:Drugs FDA approved in 2000]]
+[[Category:FDA withdrawn in 2011]]
+[[Category:FDA approved in 2017]]
+[[Category:EMA approved in 2018]]
+[[Category:Health Canada approved in 2019]]
+[[Category:PMDA approved in 2005]]