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The following table summarizes shifts in selected chemistry abnormalities by treatment arm for patients treated in ALFA-0701 . ALFA-0701 - Chemistry Laboratory Values : Shifts in Subjects with Baseline Grade 2 or Lower Values

Laboratory Abnormality

MYLOTARG + Daunorubicin + Cytarabine

Daunorubicin + Cytarabine

SUbJects ( n ) SUbJects ( n ) wlth basellne wlth basellne Progressed to

Progressed to Grade less

Grade less Grade greater Grade greater than or equal than or equal than or equal than or equal

102 102 toJ ( n , %) toJ ( n , %)

Monotherapy for Newly-Diagnosed CD33-positive AML The safety evaluation of MYLOTARG ( 6 mg / m 1 then 3 mg / m 1 , with 7 days between the doses ) as monotherapy is based on a randomized , open-label , Phase 3 trial of MYLOTARG ( N = 118 ) versus best supportive care ( BS () ( N = 119 ) in patients with previously untreated AML who were considered ineligible for intensive chemotherapy in Study AML-19 . The overall incidence of any Grade adverse reactions reported in AML-19 was 87 % in the MYLOTARG arm and 90 % in the BSC arm . The incidence of Grade greater than or equal to 3 adverse reactions was 61 % in the MYLOTARG arm and 68 % in the BSC arm . Death due to any Adverse Event was reported in the MYLOTARG arm of 19 ( 17 %) compared to the BSC arm of 23 ( 20 %).

Selected Adverse Reactions in AML-19

Any Grade Grade .:: 3 Any Grade Grade .:: 3

Monotherapy for Relapsed or Refractory CD33-positive AML The adverse reactions described in this section reflect exposure to MYLOTARG 3 mg / m 1 on Days 1 , 4 and 7 as monotherapy in 57 patients with relapsed AML treated on MyloFrance-1 . All 57 ( 100 %) patients received the 3 planned doses of MYLOTARG . During the treatment period , Grade 3 treatment-emergent adverse events ( TEAEs ) that occurred in greater than 1 % patients included sepsis ( 32 %), fever ( 16 %), rash ( 11 %), pneumonia ( 7 %), bleeding ( 7 %), mucositis ( 4 %), pain ( 4 %), diarrhea ( 2 %), headaches ( 2 %), tachycardia ( 2 %), and lung edema ( 2 %). No Grade 4 toxicity was observed . All grade TEAEs that occurred in greater than 15 % of patients included fever ( 79 %), infection ( 42 %), increased AST ( 40 %), bleeding ( 23 %), nausea and vomiting ( 21 %), constipation ( 21 %), mucositis ( 21 %), headache ( 19 %), increased ALT ( 16 %), and rash ( 16 %). No infectious deaths occurred . Grade 1 or 2 hyperbilirubinemia developed in 4 ( 7 %) patients . No episodes of VOD occurred . Seven patients received HSCT after MYLOTARG treatment . Three patients received an allogeneic BMT and 4 patients were treated with autologous BMT . No patients developed VOD following HSCT . Postmarketing Experience : The following adverse drug reactions have been identified during postapproval use of MYLOTARG . Because these reactions are reported voluntarily from a population of uncertain size , it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure . Gastrointestinal Disorders : Neutropenic colitis *; Infections and Infestations : fungal lung infections including Pulmonary mycosis and Pneumocystis jirovecii pneumonia *; and bacterial infections including Stenotrophomonas infection ; Renal and Urinary Disorders : Hemorrhagic cystitis 1 ; Respiratory, Thoracic and Mediastinal Disorders : Interstitial pneumonia . 1 (* including fatal events .) lmmunogenicity : As with all therapeutic proteins , there is potential for immunogenicity . lmmunogenicity of MYLOTARG was not studied in clinical trials using the recommended dose regimens .

USE IN SPECIFIC POPULATIONS Pregnancy : Risk Summary : Based on its mechanism of action and findings from animal studies , MYLOTARG can cause embryo-fetal harm when administered to a pregnant woman . There are no available data on MYLOTARG use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage . In rat embryo-fetal development studies , gemtuzumab ozogamicin caused embryo-fetal toxicity at maternal systemic exposures that were greater than or equal to 0.4 times the exposure in patients at the maximum recommended dose , based on AUC . If MYLOTARG is used during pregnancy , or if the patient becomes pregnant while taking MYLOTARG , advise the patient of the potential risk to a fetus . Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown . In the U . S . general population , the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4 % and 15-20 %, respectively . Data : Animal Data :

In an embryo-fetal development study in rats , pregnant animals received daily intravenous doses up to 1.2 mg / m 1 / day gemtuzumab ozogamicin during the period of organogenesis . Embryo-fetal toxicities including fetal growth retardation as evidenced by decreased live fetal weights , incidence of fetal wavy ribs and delayed skeletal ossification were observed at greater than or equal to 0.15 mg / m 1 / day . Increased embryo-fetal lethality and fetal morphological anomalies ( digital malformations , absence of the aortic arch , anomalies in the long bones in the forelimbs , misshapen scapula , absence of a vertebral centrum , and fused sternebrae ) were observed at greater than or equal to 0.36 mg / m 1 / day . All doses with embryofetal effects were observed in the presence of maternal toxicity that included decreases in gestational body weight gain , food consumption , and gravid uterine weight . The lowest dose at which embryo-fetal effects were observed in rats ( 0.15 mg / m 1 / day ) was 0.4 times the exposure in patients at the maximum recommended human dose , based on AUC . Lactation : Risk Summary : There are no data on the presence of gemtuzumab ozogamicin or its metabolites in human milk , the effects on the breastfed infant , or the effects on milk production . Because of the potential for adverse reactions in breastfed infants , women should not breastfeed during treatment with MYLOTARG and for at least 1 month after the final dose . Females and Males of Reprodudive Potential : Pregnancy Testing : Based on animal studies , MYLOTARG can cause fetal harm when administered to a pregnant woman . Verify the pregnancy status of females of reproductive potential prior to initiating MYLOTARG . Contraception : Females : Advise females of reproductive potential to avoid becoming pregnant while receiving MYLOTARG . Advise females of reproductive potential to use effective contraception during treatment with MYLOTARG and for at least 6 months after the last dose . Males : Advise males with female partners of reproductive potential to use effective contraception during treatment with MYLOTARG and for at least 3 months after the last dose . Infertility : Females : Based on findings in animals , MYLOTARG may impair fertility in females of reproductive potential . Males : Based on findings in animals , MYLOTARG may impair fertility in males of reproductive potential . Pediatric Use : The safety and efficacy of MYLOTARG in combination with daunorubicin and cytarabine have not been established in the pediatric patients with newly-diagnosed de novo AML . The safety and efficacy of MYLOTARG as a single agent in the pediatric patients with relapsed or refractory AML is supported by a single-arm trial in 29 patients in the following age groups : 1 patient 1 month to less than 2 years old , 13 patients 2 years to less than 12 years old , and 15 patients 12 years to 18 years old . A literature review included an additional 96 patients with ages ranging from 0.2 to 21 years . No differences in efficacy and safety were observed by age . Geriatric Use : Use of MYLOTARG in combination with daunorubicin and cytarabine in newly-diagnosed adult patients with de novo AML is supported by a randomized , controlled trial that included 50 patients greater than or equal to 65 years old . No overall differences in safety or effectiveness were observed between these subjects and younger subjects . Use of MYLOTARG monotherapy in newly-diagnosed adult patients with AML is supported by a randomized controlled trial with 118 patients treated with MYLOTARG . All patients were over the age of 60 years and 65 % of patients were above 75 years . No overall differences in effectiveness were observed by age . Use of MYLOTARG as single-agent treatment of relapsed or refractory AML is supported by a single-arm trial that included 27 patients 65 years or older . No overall differences in effectiveness were observed between these patients and younger patients . Elderly patients experienced a higher rate of fever and severe or greater infections .

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PATIENT OOUNSELING INFORMATION Hepatotoxicity , Including Veno-occlusive Liver Disease ( VOD ): Inform patients that liver problems , including severe , life-threatening , or fatal VOD may develop during MYLOTARG treatment . Prior to receiving MYLOTARG , inform patients who previously received , or will receive an HSCT that they may be at increased risk for developing VOD . Inform patients that the risk of developing VOD after an allogeneic HSCT is increased after receiving treatment with MYLOTARG . Inform patients that signs or symptoms of liver toxicity , including rapid weight gain , right upper quadrant pain and tenderness , hepatomegaly , and ascites should be monitored regularly during treatment , but these symptoms may not identify all patients at risk or prevent the complications of liver toxicity . Inform patients that liver problems may require dosing interruption or permanent discontinuation of MYLOTARG . Hemorrhage : Inform patients that decreased platelet counts , which may be life-threatening , may develop during MYLOTARG treatment and that complications associated with decreased platelet counts may include bleeding / hemorrhage events , which may be life-threatening or fatal . Inform patients to report signs and symptoms of bleeding / hemorrhage during treatment with MYLOTARG . Inform patients that severe bleeding / hemorrhage may require dosing interruption or permanent discontinuation of MYLOTARG . Infusion Related Readions : Advise patients to contact their health care provider if they experience signs and symptoms of infusion related reactions , including symptoms such as fever , chills , rash , or breathing problems . Pregnancy and BreasHeeding : Advise men and women of reproductive potential to use effective contraception during MYLOTARG treatment and for at least 3 and 6 months , respectively , after the last dose . Advise women of childbearing potential to avoid becoming pregnant while receiving MYLOTARG . Advise women to contact their healthcare provider if they become pregnant , or if pregnancy is suspected , during treatment with MYLOTARG . Inform the patient of the potential hazard to the fetus . Advise women against breastfeeding while receiving MYLOTARG and for 1 month after the last dose .

Rx only

This brief summary is based on MYLOTARG Prescribing Information LAB-0868-1.0 , revised September 2017 , which can be found at MylotargHCP.com .

© 2017 Pfizer Inc . All rights reserved . Printed in USA / September 2017