MOJ Immunology

Tumor Lysis Syndrome Caused by Therapeutic Monoclonal Antibodies Approved by FDA

Editorial Editorial

Volume 5 Issue 5 - 2017 In 1975, Monoclonal antibody (mAb) technique was created Physiologyby Georges or Köhler, Medicine César in Milstein,1984 for and the Nielsdiscovery. Kaj Jerne 8 years by usinglater, mouse x mouse hybridoma, they shared the Nobel Prize in Medical Director, Pharmacovigilance and Drug Safety, USA in 1992 FDA approved first therapeutic mAb Muromonab-CD3 *Corresponding author: Henry Hongrong Cai, Medical (trade name Orthoclone OKT3) to reduce acute rejection in Director, Pharmacovigilance and Drug Safety, inVentiv Health patients with organ transplants, since then, as of May 31, 2017, Clinical, 95 Cynthia Road Newton, MA 02459, USA, Tel: FDA has approved 70 therapeutic mAbs [1-3]. Among them 28 1-617-584-6628; Email: were approved for treatment of cancers (Table 1) [4-31]. These Received: June 05, 2017 | Published: June 06, 2017 therapeutic mAb targets at components expressed on cancer cell, possible mechanisms of cell lysis include complement-dependent cytotoxicity (CDC), antibody-dependent cell mediated cytotoxicity (ADCC), induced apoptosis, cancer cell growth inhibition, direct cytoxicities, and conjugates indirect effect resulting cancer cell antigensdeath (radiation chosen as or target, internalized they also derives). expressed Unfortunately, at normal socells, far there is no tumor specific antigen (TSA) available for target, those which inevitably causes various adverse reactions, in this article, Table 1 tumor lysis syndrome (TLS) is briefly reviewed.

: Monoclonal Antibodies for Cancer Therapy Approved By FDA. Drug Name Approval Date Company Active Integedients Target Indication

Rituxan 11/26/1997 IDEC CD20

Herceptin 9/25/1998 Rituximab B-NHL Mylotarg 5/17/2000 GenetechWyeth Trastuzumab EGF BreastAML Ca Campath 2/7/2001 Gemtuzumab Ozogamicin CD33CD52 Zevalin 2/19/2002 SpectrumGenzyme Alemtuzumab CD20 B-CLL 2/12/2004 Imclone Ibritumomab Tiuxetan B-NHLMCC ErbituxAvastin 2/26/2004 Cetuximab VEGFR Colon Ca 9/27/2006 GenetechAmgen Bevacizumab VEGF Colorectal Ca Vectibix 10/26/2009 Panitumumab EGFRCD20 YervoyArzera Glaxo Ofatumumab CTLA-4 MelanomaB-CLL Adcetris 3/25/20118/19/2011 SeattleBMS Sci Ipilimumab HL 6/8/2012 Brentuximab Vedotin HER2CD30 Perjeta Genetech Pertuzumab HER2 Breast Ca Kadcyla 2/22/2013 Genetech Ado-Trastuzumab Emtansine CD20 Breast Ca Gazyva 11/1/20134/21/2014 GenetechEli Eilly Obinutuzumab B-CLL Cyramza 9/4/2014 MSD Ramucirumab VEGFR2PD-1 MelanomaGastric Ca

Ketruda Amgen Pembrolizumab ALL Tositumomab; Iodine I 131 Bexxar 12/3/2014 CD19+CD3 Opdivo 12/22/2014 Tositumomab PD-1 Melanoma Unituxin UnitedBMS Terap Nivolumab 3/10/2015 Dinutuximab GD2 Neuroblastoma

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11/16/2015 Janssen MM

Darzalex 11/24/2015 Eli Eilly Daratumumab CD38 Lung cancer PortrazzaEmpliciti Necitumumab SLAMF7EGFR MM 11/30/20155/18/2016 BMS Elotuzumab PD-L1 Urothelial Ca Tecentiq 10/18/2016 Genetech Atezolizumab PD-L1 Metastatic NSCLC TecentriqLartruvo 10/19/2016 GenetechEli Eilly Atezolizumab soft tissue sarcoma EMD serono Olaratumab PDGFR-αPD-L1 Metastatic Merkel Cell Ca Bavencio 3/23/20175/1/2017 Avelumab PD-L1 Metastatic Urothelial Ca Imfinzi 5/9/2017 AstrazenecaEMD serono UK Durvalumab PD-L1 Metastatic Urothelial Ca Bavencio Avelumab

CD: Cluster of Differentiation; EGF: Epidermal Growth Factor; VEGFR: Vascular Endothelial Growth Factor Receptor; VEGF: Vascular Endothelial Growth Factor; EGFR: Epidermal Growth Factor Receptor; CTLA-4: Cytotoxic T-Lymphocyte-Associated Protein 4; HER2: Human Epidermal Growth Factor Receptor 2; PD-1: Programmed Cell Death Protein 1; GD2: Glycolipid Disialoganglioside; SLAMF7: Signaling Lymphocytic Activation Molecule Family Member 7; PD-L1: Programmed Death-Ligand 1; B-NHL: B-Cell Non-Hodgkin’s Lymphoma; AML: Acute Myeloid Leukemia; B-CLL: B-Cell Chronic Lymphocytic Leukemia; MCC: Metastatic Colorectal Carcinoma; HL: Hodgkin’s Lymphoma; ALL: Acute Lymphocytic Leukemia; MM: Multiple Myeloma; PDGFR-α: Platelet-Derived Growth Factor Receptor Alpha; MCC: Merkel Cell Carcinoma lysis prophylaxis with anti-hyperuricemics (e.g., allopurinol

TLS may be a consequence of liquid tumor treatment with Acutetherapeutic renal mAbsfailure, approved hyperkalemia, by FDA hypocalcemia, (Table 2), which hyperuricemia, is not seen withor rasburicase) hydroxyurea and or hydrationleukapheresis prior to toreduce the infusionthe peripheral of the orin thehyperphosphatemia labeling of therapeutic from tumor mAbs lysis, for solidsome tumor fatal, can (Table occur 3). therapeutic mAb. Physicians should also consider leukoreduction

white blood count to < 30,000/µL prior to administration of the tumors,within 12-24even targeting hours after same the antigen first infusionCD20, it may of the not therapeutic cause TLS therapeutic mAb. During the initial days of treatment, monitor mAbs. Interestingly among those therapeutic mABs for liquid the laboratory parameters of patients considered at risk for TLS. circulating lymphocyte count (> 25 x 109 /L) or renal impairment includingFor treatment dialysis of TLS,as indicated. correct electrolyte abnormalities, monitor are(Table at greater 2). It is risk believed for TLS patients and should with receive high tumor appropriate burden, tumor high renal function and fluid balance, and administer supportive care,

Table 2:

TherapeuticDrug Name MonoclonalApproval Antibodies Date for LiquidCompany Tumor Therapy ApprovedActive Integedients By FDA. Target Indication TLS Rituxan 11/26/1997 IDEC CD20 Yes

5/17/2000 Wyeth Rituximab* B-NHLAML Yes *MylotargCampath 2/7/2001 Gemtuzumab Ozogamicin CD33CD52 No 2/19/2002 SpectrumGenzyme Alemtuzumab CD20 B-CLL No Zevalin** 10/26/2009 Ibritumomab Tiuxetan CD20 B-NHL Yes Arzerra* 8/19/2011 SeattleGlaxo Sci Ofatumumab B-CLLHL Yes Adcetris* Brentuximab Vedotin CD20CD30 Yes Gazyva* 11/16/201511/1/2013 GenetechJanssen Obinutuzumab B-CLLMM No EmplicitiDarzalex Daratumumab SLAMF7CD38 MM No 11/30/2015 AmgenBMS Elotuzumab ALL N/A Tositumomab; Iodine I 131 Bexxar 12/3/2014 CD19+CD3 Table 3: Tositumomab

DrugTherapeutic Name MonoclonalApproval AntibodiesDate forCompany Solid Tumor Therapy ApprovedActive Integedients By FDA. Target Indication TLS Herceptin 9/25/1998 No

2/12/2004 GenetechImclone Trastuzumab** EGF BreastMCC Ca No Erbitux 2/26/2004 Cetuximab VEGFR Colon Ca No Avastin** 9/27/2006 GenetechAmgen Bevacizumab VEGF Colorectal Ca No Vectibix Panitumumab CTLA-4EGFR Melanoma No Yervoy** 3/25/2011 BMS Ipilimumab

Citation: DOI: Cai HH (2017) Tumor Lysis Syndrome Caused by Therapeutic Monoclonal Antibodies Approved by FDA. MOJ Immunol 5(5): 00169. 10.15406/moji.2017.05.00169 Copyright: Tumor Lysis Syndrome Caused by Therapeutic Monoclonal Antibodies Approved by FDA ©2017 Cai 3/3

6/8/2012 HER2 No

Perjeta** Genetech Pertuzumab HER2 Breast Ca No Kadcyla** 2/22/20134/21/2014 GenetechEli Eilly Ado-Trastuzumab Emtansine Breast Ca No Cyramza** 9/4/2014 MSD Ramucirumab VEGFR2PD-1 MelanomaGastric Ca No Keytruda** 12/22/2014 Pembrolizumab PD-1 Melanoma No Opdivo** UnitedBMS Terap Nivolumab No Unituxin** 11/24/20153/10/2015 Eli Eilly Dinutuximab GD2 NeuroblastomaLung cancer No Portrazza** Necitumumab EGFR References 16. http://www.accessdata.fda.gov/drugsatfda_docs/ 1. 17. label/2013/125427lbl.pdfhttp://www.accessdata.fda.gov/drugsatfda_docs/ Cai HH (2016) Therapeutic Monoclonal Antibodies Approved by 2. FDACai HH in 2015.(2014) MOJ Molecular Immunology Pharmacovigilance: 3(2): 87. Safety Signal for Drug 18. label/2013/125486s000lbl.pdfhttp://www.accessdata.fda.gov/drugsatfda_docs/

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Citation: DOI: Cai HH (2017) Tumor Lysis Syndrome Caused by Therapeutic Monoclonal Antibodies Approved by FDA. MOJ Immunol 5(5): 00169. 10.15406/moji.2017.05.00169