ASH Clinical News September 2017 New | Page 68

Features For Fellows & Trainees

Once you identify your focus , work to make that a career – whether it ’ s education , research , patient care , or advocacy . Imagine what your ideal job would be , then work to become the best-qualified person for that job .

Mentors can play an important role in helping you outline your ideal career and craft a focused career development plan . You need to work together to make a concrete plan for what it takes to achieve those goals – it ’ s easy to get caught up in the dreaming stage .

Are there areas you think aren ’ t emphasized enough during training ? I wish trainees were told that failure is okay and playing the long game is critical . Establishing your career is going to take time , so trainees should accept imperfect progress . If you work as hard as you can , you will make progress despite failures . Focus on your passion , realize where your deficiencies are , grow from your mistakes , and you will be successful . Not obtaining funding or having a paper rejected is part of academics . People give up on academic careers – even if it ’ s their passion – and go into private practice because they had initial failures . When you see experts in the field receiving award after award , it ’ s easy to forget that , before their successes , they experienced failures .

Trainees are also often told that there is a dichotomy between research and clinical care , and doing too much of one will make

Other notable adverse drug reactions that occurred in less than 10 % of patients treated with VYXEOS during induction or consolidation included :

• Ear and labyrinth disorders : Deafness , Deafness unilateral

• Eye Disorders : Eye conjunctivitis , Dry eye , Eye edema , Eye swelling , Eye irritation , Eye pain , Ocular discomfort , Ocular hyperemia , Periorbital edema , Scleral hyperemia

• Gastrointestinal disorders : Dyspepsia

• Psychiatric disorders : Hallucinations

• Respiratory , thoracic and mediastinal disorders : Pneumonitis

Laboratory Abnormalities All patients developed severe neutropenia , thrombocytopenia , and anemia . See Table 3 for the incidences of Grade 3 thrombocytopenia and Grade 4 neutropenia that were prolonged in the absence of active leukemia .

Table 3 : Prolonged Cytopenias for Patients in Study 1 Induction 1 Consolidation 1 b

VYXEOS N = 58 n (%)

7 + 3 N = 34 n (%)

VYXEOS N = 48 n (%)

5 + 2 N = 32 n (%)

a

Platelets < 50 Gi / L or neutrophils < 0.5 Gi / L lasting past cycle day 42 in the absence of active leukemia . b

Patients receiving at least 1 consolidation .

Grade 3-4 chemistry abnormalities occurring in greater than 5 % of VYXEOS treated patients in Study 1 are presented in Table 4 .

Table 4 : Grade 3-4 a Chemistry Abnormalities ≥5 % of VYXEOS Treated Patients in Study 1

Induction Consolidation

VYXEOS N = 153 n (%)

Chemistry Abnormalities

7 + 3 N = 151 n (%)

VYXEOS N = 49 n (%)

5 + 2 N = 32 n (%)

DRUG INTERACTIONS

Cardiotoxic Agents Concomitant use of cardiotoxic agents may increase the risk of cardiotoxicity . Assess cardiac function more frequently when VYXEOS is coadministered with cardiotoxic agents [ see Warnings and Precautions ].

Hepatotoxic Agents Concomitant use with hepatotoxic agents may impair liver function and increase the toxicity of VYXEOS . Monitor hepatic function more frequently when VYXEOS is coadministered with hepatotoxic agents .

USE IN SPECIFIC POPULATIONS

Pregnancy

Risk Summary Based on anecdotal data of cytarabine in pregnant women and results of studies of daunorubicin and cytarabine in animals , VYXEOS can cause embryo-fetal harm when administered to a pregnant woman . There are no adequate and well-controlled studies of VYXEOS , daunorubicin , or cytarabine in pregnant women . Daunorubicin and cytarabine are reproductive and developmental toxicants in multiple species ( mice , rats , and / or dogs ), starting at a dose that was approximately 0.02 times the exposure in patients at the recommended human dose on a mg / m 2 basis [ see Animal Data ]. Patients should be advised to avoid becoming pregnant while taking VYXEOS . If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug , apprise the patient of the potential harm to a fetus .

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown . Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications . In the U . S . general population , the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4 % and 15 to 20 %, respectively .

Data

Human Data Cytarabine can cause fetal harm if a pregnant woman is exposed to the drug . Four anecdotal cases of major limb malformations have been reported in infants after their mothers received intravenous cytarabine , alone or in combination with other agents , during the first trimester .

Animal Data A liposomal formulation of daunorubicin was administered to rats on gestation days 6 through 15 at 0.3 , 1.0 , or 2.0 mg / kg / day ( about 0.04 , 0.14 , or 0.27 the recommended human dose on a mg / m 2 basis ) and produced severe maternal toxicity and embryolethality at 2.0 mg / kg / day and was embryotoxic and caused fetal malformations ( anophthalmia , microphthalmia , incomplete ossification ) at 0.3 mg / kg / day . Embryotoxicity was characterized by increased embryo-fetal deaths , reduced numbers of litters , and reduced litter sizes .

Cytarabine was teratogenic in mice ( cleft palate , phocomelia , deformed appendages , skeletal abnormalities ) when doses ≥2 mg / kg / day were administered IP during the period of organogenesis ( about 0.06 times the recommended human dose on a mg / m 2 basis ), and in rats ( deformed appendages ) when 20 mg / kg was administered as a single IP dose on day 12 of gestation ( about 1.2 times the recommended human dose on a mg / m 2 basis ). Single IP doses of 50 mg / kg in rats ( about 3 times the recommended human dose on a mg / m 2 basis ) on day 14 of gestation reduced prenatal and postnatal brain size and permanent impairment of learning ability .

Cytarabine was embryotoxic in mice when administered during the period of organogenesis . Embryotoxicity was characterized by decreased fetal weight at 0.5 mg / kg / day ( about 0.02 times the recommended human dose on a mg / m 2 basis ), and increased early and late resorptions and decreased live litter sizes at 8 mg / kg / day ( about 0.24 times the recommended human dose on a mg / m 2 basis ).

Lactation

Risk Summary There are no data on the presence of daunorubicin , cytarabine , or their metabolites in human milk , their effects on the breastfed infant , or their effects on milk production . Because of the potential for serious adverse reactions in breastfed infants , advise lactating women not to breastfeed during treatment with VYXEOS and for at least 2 weeks after the last dose .