FDA Approval: Gemtuzumab Ozogamicin for the Treatment of Adults with Newly Diagnosed CD33-Positive Acute Myeloid Leukemia

被引：152

作者：

Jen, Emily Y. ^{[1
]}

Ko, Chia-Wen ^{[1
]}

Lee, Jee Eun ^{[1
]}

Del Valle, Pedro L. ^{[1
]}

Aydanian, Antonina ^{[1
]}

Jewell, Charles ^{[1
]}

Norsworthy, Kelly J. ^{[1
]}

Przepiorka, Donna ^{[1
]}

Nie, Lei ^{[1
]}

Liu, Jiang ^{[1
]}

Sheth, Christopher M. ^{[1
]}

Shapiro, Marjorie ^{[1
]}

Farrell, Ann T. ^{[1
]}

Pazdur, Richard ^{[1
]}

机构：

[1] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA

来源：

CLINICAL CANCER RESEARCH | 2018年 / 24卷 / 14期

关键词：

SURVIVAL; INDUCTION; EFFICACY; PHASE-3; TRIALS;

D O I：

10.1158/1078-0432.CCR-17-3179

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

On September 1, 2017, the FDA granted approval for gemtuzumab ozogamicin (Mylotarg; Pfizer Inc.) in combination with daunorubicin and cytarabine and as a monotherapy for the treatment of adult patients with newly diagnosed CD33-positive acute myeloid leukemia (AML). Gemtuzumab ozogamicin is a CD33-targeted antibody-drug conjugate joined to calicheamicin. Approval of gemtuzumab ozogamicin combination treatment was based on a randomized trial of 271 patients with newly diagnosed AML treated with daunorubicin and cytarabine with or without 3 mg/m(2) fractionated gemtuzumab ozogamicin, which resulted in an event-free survival (EFS) of 13.6 months for gemtuzumab ozogamicin+horndaunorubicin and cytarabine and 8.8 months for daunorubicin and cytarabine alone [HR = 0.68 (95% confidence interval (CI), 0.51-0.91)]. Hemorrhage, prolonged thrombocytopenia, and veno-occlusive disease were serious toxicities that were more common in patients treated with gemtuzumab ozogamicin + daunorubicin and cytarabine. Approval of gemtuzumab ozogamicin monotherapy was based on a randomized trial of 237 patients with newly diagnosed AML treated without curative intent. Median overall survival (OS) was 4.9 months with gemtuzumab ozogamicin versus 3.6 months on best supportive care [HR = 0.69 (95% CI, 0.53-0.90)]. Adverse events were similar on both arms. Postapproval, several studies are required including evaluation of fractionated gemtuzumab ozogamicin pharmacokinetics, safety of combination gemtuzumab ozogamicin in the pediatric population, immunogenicity, and the effects of gemtuzumab ozogamicin on platelet function. (C) 2018 AACR.

引用

页码：3242 / 3246

页数：5

共 14 条

[1] End points to establish the efficacy of new agents in the treatment of acute leukemia [J].

Appelbaum, Frederick R. ;

Rosenblum, Daniel ;

Arceci, Robert J. ;

Carroll, William L. ;

Breitfeld, Philip P. ;

Forman, Stephen J. ;

Larson, Richard A. ;

Lee, Stephanie J. ;

Murphy, Sharon B. ;

O'Brien, Susan ;

Radich, Jerald ;

Scher, Nancy S. ;

Smith, Franklin O. ;

Stone, Richard M. ;

Tallman, Martin S. .

BLOOD, 2007, 109 (05) :1810-1816

[2] Addition of Gemtuzumab Ozogamicin to Induction Chemotherapy Improves Survival in Older Patients With Acute Myeloid Leukemia [J].

Burnett, Alan K. ;

Russell, Nigel H. ;

Hills, Robert K. ;

Kell, Jonathan ;

Freeman, Sylvie ;

Kjeldsen, Lars ;

Hunter, Ann E. ;

Yin, John ;

Craddock, Charles F. ;

Dufva, Inge Hoegh ;

Wheatley, Keith ;

Milligan, Donald .

JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (32) :3924-3931

[3] Identification of Patients With Acute Myeloblastic Leukemia Who Benefit From the Addition of Gemtuzumab Ozogamicin: Results of the MRC AML15 Trial [J].

Burnett, Alan K. ;

Hills, Robert K. ;

Milligan, Donald ;

Kjeldsen, Lars ;

Kell, Jonathan ;

Russell, Nigel H. ;

Yin, John A. L. ;

Hunter, Ann ;

Goldstone, Anthony H. ;

Wheatley, Keith .

JOURNAL OF CLINICAL ONCOLOGY, 2011, 29 (04) :369-377

[4] Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study [J].

Castaigne, Sylvie ;

Pautas, Cecile ;

Terre, Christine ;

Raffoux, Emmanuel ;

Bordessoule, Dominique ;

Bastie, Jean-Noel ;

Legrand, Ollivier ;

Thomas, Xavier ;

Turlure, Pascal ;

Reman, Oumedaly ;

de Revel, Thierry ;

Gastaud, Lauris ;

de Gunzburg, Noemie ;

Contentin, Nathalie ;

Henry, Estelle ;

Marolleau, Jean-Pierre ;

Aljijakli, Ahmad ;

Rousselot, Philippe ;

Fenaux, Pierre ;

Preudhomme, Claude ;

Chevret, Sylvie ;

Dombret, Herve .

LANCET, 2012, 379 (9825) :1508-1516

[5] Addition of Gemtuzumab Ozogamycin to Chemotherapy Improves Event-Free Survival but Not Overall Survival of AML Patients with Intermediate Cytogenetics Not Eligible for Allogeneic Transplantation. Results of the GOELAMS AML 2006 IR Study [J].

Delaunay, Jacques ;

Recher, Christian ;

Pigneux, Arnaud ;

Witz, Francis ;

Vey, Norbert ;

Blanchet, Odile ;

Lefebvre, Pascale ;

Luquet, Isabelle ;

Guillerme, Isabelle ;

Volteau, Christelle ;

Gyan, Emmanuel ;

Lioure, Bruno ;

Jourdan, Eric ;

Bouscary, Didier ;

Guieze, Romain ;

Randriamalala, Edouard ;

Uribe, Mario E. Ojeda ;

Dreyfus, Francois ;

Lacombe, Catherine ;

Bene, Marie-christine ;

Cahn, Jean-Yves ;

Harousseau, Jean-Luc ;

Ifrah, Norbert .

BLOOD, 2011, 118 (21) :37-38

[6] An update of current treatments for adult acute myeloid leukemia [J].

Dombret, Herve ;

Gardin, Claude .

BLOOD, 2016, 127 (01) :53-61

[7]

Kieffer L., 2000, CLIN PHARM BIOPHARMA

[8]

NORSWORTHY KJ, 2018, ONCOLOGIST

[9] A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia [J].

Petersdorf, Stephen H. ;

Kopecky, Kenneth J. ;

Slovak, Marilyn ;

Willman, Cheryl ;

Nevill, Thomas ;

Brandwein, Joseph ;

Larson, Richard A. ;

Erba, Harry P. ;

Stiff, Patrick J. ;

Stuart, Robert K. ;

Walter, Roland B. ;

Tallman, Martin S. ;

Stenke, Leif ;

Appelbaum, Frederick R. .

BLOOD, 2013, 121 (24) :4854-4860

[10] Sequential influences of leukemia-specific and genetic factors on P-glycoprotein expression in blasts from 817 patients entered into the National Cancer Research Network acute myeloid leukemia 14 and 15 trials [J].

Seedhouse, Claire H. ;

Grundy, Martin ;

White, Paul ;

Li, Yun ;

Fisher, Janet ;

Yakunina, Darya ;

Moorman, Anthony V. ;

Hoy, Terence ;

Russell, Nigel ;

Burnett, Alan ;

Pallis, Monica .

CLINICAL CANCER RESEARCH, 2007, 13 (23) :7059-7066

← 1 2 →