Clinical Pearls of PD1/PDL1 Inhibitors UNMH Pharmacy Residents - - PDF document

10/4/18 1

Clinical Pearls

UNMH Pharmacy Residents Jessica Lewis-Gonzalez, PharmD Valentin Pacuraru, PharmD Amre Elmaoued, PharmD Siena Meador, PharmD Ngoc-Yen Pham, PharmD

Management of Adverse Effects

• f PD1/PDL1 Inhibitors

Jessica Lewis-Gonzalez, PharmD PGY-1 Pharmacy Resident University of New Mexico Hospitals

Objectives

¡ Pharmacist § Evaluate and assess the

management of adverse effects of the PD1/PDL1 inhibitors

¡ Technician § Identify management of

adverse effects of the PD1/PDL1 inhibitors

Wait…which drugs are those again???

¡ PD1 Inhibitors § Pembrolizumab

(Keytruda)

§ Nivolumab (Opdivo) ¡ PDL1 Inhibitors § Atezolizumab (Tecentriq) § Avelumab (Bavencio) § Durvalumab (Imfinzi)

• These are IV cancer chemotherapy medications that are

administered most commonly in the outpatient setting at infusion centers.

Why is this important to you? Adverse Events to be Aware of:

¡ Immune related adverse events § Dermatologic § GI § Hepatic § Endocrine § Other less common inflammatory events

• Postcow. Jour Clin Onc. 2015.

10/4/18 2 Grading of Adverse Events

¡ Per Common Terminology Criteria for Adverse Events (CTCAE):

NIH,NCI. Common Terminology Criteria for Adverse Events V. 5.0. 2017.

Treatment of Adverse Events (In General)

¡

Grade 1: Mild, asymptomatic

§ Management: Observation, intervention not needed ¡

Grade 2: Moderate

§ Management: Local or noninvasive intervention indicated § Will likely need low-dose oral prednisone /methylprednisolone and may be

able to continue treatment

¡

Grade 3: Several or medically significant but not immediately life- threatening

§ Management: Stop immunotherapy, hospitalization indicated, high dose

prednisone /methylprednisolone

¡

Grade 4: Life-threatening consequences

§ Management: Urgent intervention, will permanently stop immunotherapy ¡

Grade 5: Death related to AE

NIH,NCI. Common Terminology Criteria for Adverse Events V. 5.0. 2017.

Derm Adverse Event - Maculopapular Rash

Grade Hold Immunotherapy Steroids Antihistamine Other 1 Moderate-potency topical Topical emollient 2 Consider holding High-potency topical AND/OR low-dose prednisone /methylprednisolone Topical emollient 3/4 High-potency topical + low-dose prednisone /methylprednisolone (increase dose if no improvement) Urgent Derm Consult

• NCCN. Management of Immunotherapy-Related Toxicities(Version 1.2018).

GI Adverse Event- Diarrhea/Colitis

Grade Hold Immunotherapy Steroids Permanently DC Other

1

Consider holding Loperamide, hydration

2

IV methylprednisolone 1mg/kg/day

3

(consider resuming after resolution) IV methylprednisolone 2mg/kg/day Consider Inpatient Supportive Care

4

IV methylprednisolone 2 mg/kg/day Consider Inpatient Supportive Care

(NCCN). Management of Immunotherapy-Related Toxicities(Version 1.2018).

Hepatic Adverse Event- Acute Pancreatitis

Grade Hold Immunotherapy Steroids Permanently DC Other

1

Consider Gastroenterology Referral

2

Low-dose prednisone/ methylprednisolone

3/4

High-dose prednisone/ methylprednisolone

(NCCN). Management of Immunotherapy-Related Toxicities(Version 1.2018).

10/4/18 3 Low-dose vs High-dose steroids

¡ Low-dose corticosteroids for grade 2: § prednisone or methylprednisolone 0.5–1 mg/kg/day ¡ High-dose corticosteroids for grade 3 and 4: § prednisone or methylprednisolone 1–2 mg/kg/day ¡ Tapering off systemic corticosteroids over 4–6 weeks after

symptoms have resolved to Grade 1 or 2

Rudzki, JD. Memo Springer. 2018.

Summary

¡ When it comes to immune-related adverse events with

checkpoint inhibitors – Steroids are your friends!

§ Topical § Low-dose § High-dose ¡ When patients present to the hospital on a PD-1/PDL-1

inhibitor with an acute event:

§ Consider drug as a potential cause § Grade the reaction (if caused by drug) § Treat based on grading

Approach to the Patient with Nausea & Vomiting and QTc Prolongation

Valentin Pacuraru, PharmD PGY-1 Pharmacy Resident University of New Mexico Hospitals

Learning Objectives

Pharmacists

• Define the

extent of QTc prolonging effect of several N/V medications.

Technicians

• Identify the

five most commonly used drugs for N/V that impact QTc.

QTc Prolongation and risk of Torsades de Pointes Torsades

https://pedemmorsels.com/prolonged-qtc/

Defining QTc Prolongation

QTc Values by Age and Sex (ms) 1 – 15 y/o Adult Males Adult Females Normal <440 ms <430 ms <450 ms Borderline 440 – 460 ms 430 – 450 ms 450 – 470 ms Prolonged >460 ms >450 ms >470 ms

• >500 ms

Clinically Significant QTc Prolongation

10/4/18 4 Torsades de Pointes Risk Factors

¡ Female Sex ¡ Hypokalemia and/or Hypomagnesemia ¡ Bradycardia ¡ Recent Cardioversion ¡ Structural Heart Disease ¡ Digoxin Therapy ¡ Baseline QT Prolongation ¡ Rapid IV infusion of QT prolonging medications ¡ Pharmacokinetic Interactions

Li M. P T. 2017 Lin YL. Pharmacoepidemiol Drug Saf. 2009

Risk Scoring Option

Tisdale Risk Score

Risk Factor Points QTc Interval Risk Stratification Age >68 1 Risk Category Risk Score Female Gender 1

Low <7

Loop Diuretic 1 Potassium <3.5 mEq 2 QTc >450 on Admit 2

Moderate 7 – 10

Acute MI 2 2+ QTc Prolonging Drugs 3 Sepsis 3

High >11

Heart Failure 3 One QTc Prolonging Med 3 Maximum Risk Score 21

Tisdale JE. Can Pharm J 2016

Approaching Nausea and Vomiting

Gastroparesis Infectious Medication Induced Electrolyte or Fluid Abnormality GI Obstruction/Inflammation GERD Diabetes Related

Treat the Underlying Etiology First

Common Inpatient Medications for Nausea and Vomiting

Ondansetron Promethazine Prochlorperazine Metoclopramide Haloperidol Trimetho- benzamide Olanzapine

Alternate Agents for Nausea & Vomiting

Dexamethasone

• Best data for PONV and CINV
• Side effects limit use in simple N/V

Inhaled Isopropyl Alcohol

• Promising ED data including superiority to ondansetron

Benzodiazepines

• Most appropriate for withdrawal, anxiety, and anticipatory related nausea

April MD et al. Ann Emerg Med 2018 Beadle KL. Ann Emerg Med. 2016

Haloperidol

D2 Receptor Antagonist Published evidence

• f QTc prolongation

ranging from 8 ms – 35 ms Multiple publications of torsadogenesis and cardiac dysrhythmia IM, IV, Sol, and Tab

Wenzel-seifert K. Dtsch Arztebl Int. 2011 Van noord C . J Clin Psychopharmacol. 2009

10/4/18 5 Ondansetron

Serotonin-3 Receptor Antagonist Published evidence of QTc prolongation ranging from 4 ms – 32 ms Few published cases

• f torsades or

dysrhythmia, but associated high IV doses (32 mg) IV, IM, Sol, Tab, ODT, and PO Film

Brygger L. Expert Opin Drug Saf. 2014 Poluzzi E. PLoS ONE 10. 2015

Promethazine

H1 and D2 Receptor Antagonist Published Evidence

• f QTc prolongation

Low torsadogenic potential IM, IV, PR, Sol, and Tab available

Jo SH. . Pharmacol Res. 2009 Owczuk R. Anaesthesia. 2009

Metoclopramide

D2 Receptor Antogonist Published evidence of QTc prolongation Few published case reports of cardiac decompensation IV, IM, Sol, Tab, and ODT

Smith HS. Ann Palliat Med. 2012 Smith HS. Ann Palliat Med 2012 Chou CC Chang Gung Med J 2001 Ellidokuz E. Aliment Pharmacol Ther. 2003

Prochlorperazine

D2 Receptor Antagonist Published evidence

• f QTc

prolongation, particularly in vitro Few case reports of prochlorperazine contributing to an arrhythmia IM,IV, PR, Sol, and Tab

Aström-lilja C. Pharmacoepidemiol Drug Saf. 2008

Olanzapine

D2 Receptor Antagonist Published evidence

• f QTc prolongation

Few case reports of torsades with IV formulation PO, IM, and IV forms available

Czekalla J. J Clin Psychiatry. 2001 Suzuki Y. Human Psychopharmacology. 2011 Lam YWF. Brown University Psychopharmacology . 2015

Trimethobenzamide

D2 Receptor Antagonist No published evidence of QTc prolongation No published evidence of torsadogenesis PO and IM forms available

10/4/18 6 Ranking Torsadogenic Risk

7) Trimethobenzamide 6) Prochlorperazine 5) Metoclopramide 4) Olanzapine 3) Promethazine 2) Ondansetron 1) Haloperidol

Isbister GK. Br J Clin Pharmacol. 2013

Final Thoughts

• No one size fits all answer
• QTc prolongation ≠ torsadogenic risk
• Additional risk factors are important
• Risk/Benefit is a patient specific decision
• Medication choice should be based on risk/benefit,

patient specific characteristics, and route

Alternative Uses of Haloperidol

Amre Elmaoued, PharmD PGY-1 Pharmacy Resident University of New Mexico Hospitals

Objectives

¡ Pharmacists: § Evaluate some alternative uses of haloperidol ¡ Technicians: § Identify some off-label uses of haloperidol

Haloperidol - D2 Antagonist

¡ 1st generation

Antipsychotic (a.k.a. Typical Antipsychotic)

¡ FDA Indication: § Psychosis § Schizophrenia ¡ Typical Dosing: 0.5-2 mg

two- three times daily

Mechanism of Action

Psychopharmacology Institute. (n.d.)

Haloperidol - Characteristics

Psychopharmacology Institute. (n.d.)

D2 Activity High 5HT2 Activity Medium Muscarinic Activity Low Alpha-1 adrenergic Activity Low Antihistamine Activity Low

10/4/18 7 IM Lactate for IV

Brief Psych Rating Scale Baseline 4 Hours 24 Hours Diazepam 28.5 11.4 6.3 Haloperidol 30.5 3.8 8

¡

Lerner et. al. (1978):

§ Randomized 40 patients to haloperidol or diazepam § Both received via IV route ¡

FDA Warning (2007):

§ Increased risk of QTc prolongation has been seen § Studies are showing lower dose, <2mg, no increased QTc ¡

Both equally effective antipsychotics

¡

Doses

§ Haloperidol = 15mg start. 10mg q 1hr. Total average ~ 20-35mg § Diazepam = 10-15 mg start. 5-10mg q1hr. Total ~30-40mg

¡

More withdrawal associated with haloperidol

Duprey M. S,Int Car Med. 2016 Lerner, Y. Am of Psy. 1979 Hatta, K. J Clin Psy. 2001

Off-Label Uses

• Intractable headaches
• Agitation/Rapid Tranquilization
• Nausea/Vomiting
• Intractable hiccups
• Chorea of Huntington disease
• Delirium in the ICU
• Obsessive-compulsive disorder

Intractable Headaches

¡

Compared haloperidol 5mg IV

• vs. metoclopramide 10mg IV

§

Emergency Department, N= 64

▪ 31 haloperidol ▪ 33 metoclopramide

¡

All patients were pretreated with diphenhydramine 25mg

¡

VAS measured 0, 20, 40, 60, 80 min

Gaffigan, M. E., J Emerg Med. 2015

Agitation/Rapid Tranquilization

¡ Dose: haloperidol lactate 2.5mg-10 mg IM

Ostinelli, E. G. et al. Cochrane Database Syst Rev. 2017

Nausea/Vomiting

¡ Usual Dose: 0.5mg - 2.5mg QD or BID ¡ Studied in: § Cancer § Palliative Care § Post-Operative Nausea and Vomiting

Nausea/Vomiting

Response Complete Response Partial Response No Response Failure Patient-rated Day 2 (n = 33)

8 12 10 3

Patient-rated Day 5 (n = 23)

7 10 2 4

Observer-rated Day 2 (n = 29)

8 15 4 2

Observer-rated Day 5 (n = 19)

6 9 3 1

Adapted from Hardy, J. R., et al. J Pain Symptom Manage. 2010.

10/4/18 8 Nausea/Vomiting

Response Response (CR + PR) n/N(%) Response (All Patients) n/N(%)

Patient-rated Day 2 (n = 33)

20/33 (60) 20/42 (47)

Patient-rated Day 5 (n = 23)

17/23 (74) 17/42 (40)

Observer-rated Day 2 (n = 29)

23/29 (79) 23/42 (54)

Observer-rated Day 5 (n = 19)

15/19 (78) 15/42 (35)

Adapted from Hardy, J. R., et al. J Pain Symptom Manage. 2010.

Side Effects

TRANSLATES TO

Extrapyramidal Side Effects Very High Anticholinergic Effects Very Low Hypotensive Effects Very Low Sedating Effects Very Low D2 Activity High 5HT2 Activity Medium Muscarinic Activity Low Alpha-1 adrenergic Activity Low Antihistamine Activity Low

Side Effects- QTc Prolongation

RISK FACTORS CONSIDERATIONS

¡

Baseline ECG

¡

If giving IV haloperidol, monitor ECG closely

¡

Discontinue multiple medications with QTc prolongation

¡

QTc > 500ms à considered risk for TdP

§

>450ms for males à considered prolonged

§

>470ms for females

Unmodifiable risk factors Potentially modifiable risk factors Female Gender Hypokalemia or severe hypomagnesaemia Increasing age Bradycardia Genetically long QT syndrome Family history of sudden death History of previous drug- induced QT prolongation > 1 QTc prolonging medication Meds that cause electrolyte abnormalities or may cause renal or hepatic dysfunction Structural heart disease/LV dysfunction Starvation or obesity Impaired elimination due to renal or hepatic disease High drug concentrations due to overdose or rapid IV administration

Rapid Update: Recently Approved Antimicrobials

Siena Meador, PharmD PGY-1 Pharmacy Resident University of New Mexico Hospitals

Objectives

¡ Pharmacist: § Discuss the role of recently approved antimicrobial

therapies

¡ Technician: § Identify recently approved antimicrobial therapies

Baxdela™ delafloxacin

https://jamanetwork.com/journals/jama/article-abstract/2646700

10/4/18 9 FDA Approved Indications

¡ Fluoroquinolone for

the treatment of acute bacterial skin and skin structure infections (ABSSSI) in adults ≥18 years old

Baxdela™ (delafloxacin) [package insert]. 2017.

K. pneumoniae

P.

aeruginosa

• E. coli

E. faecalis

Certain Staphylococcus spp. Certain Streptococcus spp.

Dosing

¡ By mouth § 450 mg tablet every 12 hours § Not renally adjusted § Without regard to food ¡ Intravenous eGFR Dose Interval ≥30 300 mg 12 hours 15-29 200 mg 12 hours <15 or dialysis Not recommended, consider switching to tablet

Baxdela™ (delafloxacin) [package insert]. 2017.

Warnings/Adverse Effects

¡ Black Box Warnings § Tendinitis/tendon rupture § Peripheral neuropathy § Central nervous system effects § Exacerbation of muscle weakness in myasthenia gravis ¡ Contraindication § Hypersensitivity ¡ Warnings § C. difficile-associated diarrhea § Drug-resistant bacteria ¡ Adverse Reactions § Nausea (8%) § Diarrhea (8%) § Headache (3%) § Transaminase elevations (3%) § Vomiting (2%) ¡ Requires a medication guide

Baxdela™ (delafloxacin) [package insert]. 2017.

Place in Therapy

¡ Limited benefit over other fluoroquinolones but more

expensive

¡ Most skin and skin structure infections are caused by Gram

positive bacteria

¡ Gram negative coverage is not usually indicated

Vabomere™ meropenem/vaborbactam

http://www.vabomere.com

FDA Approved Indications

¡ Carbapenem + β-

lactamase inhibitor for the treatment of complicated UTI, including pyelonephritis, in adults ≥18 years old

Vabomere™ (meropenem and vaborbactam) [package insert] 2017.

K. pneumoniae Enterobacter cloacae spp

• E. coli

10/4/18 10 Dosing

¡ Intravenous ¡ Only compatible with normal saline ¡ All doses are administered over 3 hours eGFR Dose Interval Minimum diluent ≥50 4 gm 8 hours 250 mL 30-49 2 gm 8 hours 125 mL 15-29 2 gm 12 hours 125 mL <15 or dialysis 1 gm 12 hours 70 mL

Vabomere™ (meropenem and vaborbactam) [package insert]. 2017.

Warnings/Adverse Effects

¡ Contraindication § Hypersensitivity (1.8%) ¡ Warnings § Seizures § Other CNS experiences § Neuromotor impairment § Reduced valproic acid levels § Thrombocytopenia § C. difficile-associated diarrhea § Drug-resistant bacteria ¡ Adverse effects § Headache (8.8%) § Phlebitis/infusion reactions (4.4%) § Diarrhea (3.3%) § Nausea (1.8%) § Transaminase elevations (1.8%) § Pyrexia (1.5%) § Hypokalemia (1.1%)

Vabomere™ (meropenem and vaborbactam) [package insert]. 2017.

Place in Therapy

¡ Carbapenem-resistant enterobacteriaceae (CRE) ¡ Does NOT have improved efficacy against multidrug resistant

Pseudomonas spp. or Acinetobacter spp.

¡ Limited by dosing and administration requirements

Solosec™ secnidazole

https://www.solosec.com

FDA Approved Indications

¡ Nitroimidazole for

the treatment of bacterial vaginosis in women ≥18 years old

Solosec™ (secnidazole) [package insert]. 2017.

Bacteriodes spp. Gardnerella vaginalis Prevotella spp. Mobiluncus spp. Megasphaera- like type I/II

Dosing

¡ Single dose of 2 grams (1 packet) ¡ Sprinkle over applesauce, yogurt, or pudding ¡ Consume within 30 minutes ¡ Do not chew or crunch the granules ¡ May be followed with a glass of water ¡ Do NOT dissolve in any liquid

Solosec™ (secnidazole) [package insert]. 2017.

10/4/18 11 Warnings/Adverse Effects

¡ Contraindication § Hypersensitivity ¡ Warnings § Vulvo-vaginal candidiasis (9.6%) § Risk for carcinogenicity § Drug resistance ¡ Adverse effects § Headache (3.6%) § Nausea (3.6%) § Dysgeusia (3.4) § Vomiting (2.5%) § Diarrhea (2%) § Abdominal pain (2%) § Vulvovaginal pruritus (2%)

Solosec™ (secnidazole) [package insert]. 2017.

Place in Therapy

¡ Only single-dose treatment for bacterial vaginosis ¡ Beneficial for patients with adherence concerns ¡ May be useful in hospital-owned outpatient clinics

SHINGRIX™ Zoster Vaccine Recombinant, Adjuvanted

https://www.shingrix.com/index.html

FDA Approved Indication/Dosing

¡ For the prevention of herpes zoster in adults ≥50 years old ¡ Two vaccine series, 2 to 6 months apart ¡ 0.5 mL injected intramuscularly ¡ 2 vials per injection ¡ Keep refrigerated, do not freeze

Image from gsksource

Warnings/Adverse Effects

¡ Contraindication § Severe allergic reaction to any component or after a previous dose ¡ Local reactions § Pain (78%) § Redness (38.1%) § Swelling (25.9%) ¡ General reactions § Myalgia (44.7%) § Fatigue (44.5%) § Headache (37.7%) § Shivering (26.8%) § Fever (20.5%) § GI symptoms (17.3%)

SHINGRIX™ (Zoster Vaccine Recombinant, Adjuvanted) [package insert]. 2017.

Place in Therapy

¡ Advisory Committee on Immunization Practices (ACIP): § Vaccinate all immunocompetent patients ≥50 years old § Recombinant herpes zoster is preferred over the live zoster vaccine § Adults previously vaccinated with the live zoster vaccine should be revaccinated with Shingrix

Dooling KL, et al. Recommendations of the Advisory Committee on Immunization Practices for Use of Herpes Zoster Vaccines.

10/4/18 12

Prevention of Hepatitis B reactivation in patients receiving Rituxan therapy

Ngoc-Yen Pham, PharmD. PGY-1 Pharmacy Resident University of New Mexico Hospitals

Learning Objectives

¡ Pharmacists: § Formulate an appropriate recommendation to manage patients

with Hepatitis B who require immunotherapy management with Rituxan

¡ Technicians: § Identify the therapies used to manage patients with Hepatitis B

who require immunotherapy management with Rituxan

Rituxan (rituximab)

Indications Monoclonal antibody Boxed warnings

Non-Hodgkin Lymphoma Chronic Lymphocytic Leukemia ( CLL) Rheumatoid arthritis Vasculitis

Anti-CD20 directed

• n B-lymphocytes

Infusion reaction Mucocutaneous Reactions Hepatitis B Reactivation Progressive Multifocal leukoencephalopathy

Rituxan (rituximab) [prescribing information].

Hepatitis B Virus (HBV) Serology

§ IgM antibody to HBV core antigen § Indicates recent/acute HBV infection in ≤6 months § HBV surface antigen § Indicates a person is infectious

HBsAg

§ Antibody to HBV surface antigen § Indicates immunity

Anti-HBs

§ IgG antibody to HBV core antigen § Marker of past or current infection with HBV

IgM Anti-HBc

§ Total antibody to HBV core antigen § Indicates exposure to HBV § Correlates with the levels of HBV virus particles § Marker of HBV replication and infection § HBV e antigen § Marker of HBV replication and infection

HBeAg Anti-HBc IgG Anti-HBc HBV DNA

Risk factors for HBV reactivation (HBVr)

¡ HBV-DNA level ¡ Anthracyclines/steroid use ¡ Transplantation ¡ Presence of lymphoma § Male gender § Lack of HBs antibody § HBsAg positive § Presence of precore mutant

Tsutsumi Y. World J Hepatol. 2013.

Prophylactic antiviral therapy Prophylactic antiviral therapy Or monitoring Monitoring High Moderate Low

Management of HBV reactivation

Screen patients before immunosuppressive therapy HBsAg+ Anti-HBc + HBsAg- Anti-HBc + HBsAg- Anti-HBc- Check HBV DNA Assess Risk

Hwang J, Nat Rev Gastroenterol Hepatol. 2014. Perrillo R. Gastroenterology. 2015. Pattullo V. Clin Mol Hepatol. 2016.

vaccinations

10/4/18 13 Risk Stratification for HBVr

Risk Groups HBVr drug estimates

High-risk groups (>10%) B-cell depleting agents

• Rituximab
• Ofatumumab

Anthracycline derivatives

• Doxorubicin
• Epirubicin

Corticosteroids therapy ≥ 4 weeks (prednisone 20mg) Medium risk group (1% - 10%) TNF –α inhibitors Cytokines and integrin inhibitors Tyrosine kinase inhibitors Low-risk groups (<1%) Azathioprine, 6-mercaptopurine Methotrexate Intra-articular corticosteroids

Perrillo R. Gastroenterology. 2015. Hwang J, Nat Rev Gastroenterol Hepatol. 2014. Pattullo V. Clin Mol Hepatol. 2016.

Prophylactic Antiviral therapy

Resistance Class Boxed warning: lactic acidosis and severe hepatomegaly with steatosis, acute exacerbation of HBV upon discontinuation

Lamivudine

Low barrier to resistance Mutation and resistance

Entecavir

Higher barrier

• f resistance

Renal dose adjustments

Tenofovir

Higher barrier

• f resistance

Renal dose adjustments nephrotoxicity

Han S. J Am Board Fam Med. 2015. Lampertico P. J Hepatol. 2017.

Concerns

Prophylaxis versus Pre-emptive therapy

Reference) Antivirals vs controls (n) Antiviral timing Reactivation rates Lau et al.(2003) lamivudine vs pre-emptive treatment 1 week before chemotherapy or deferred until serological evidence

• f HBV

0% verus 53% (P = 0.002) Hsu et al.(2008) lamivudine vs pre-emptive treatment On day 1 of chemotherapy and until 2 months after or started on treatment if ALT levels >1.5xULN 11.5% versus 56% (P = 0.001) Huang et al.(2013) entecavir vs pre- emptive treatment Before chemotherapy to 3 months after or at the time of HBV reactivation At months 6, 12, and 18 0%, 0%, and 4.3% in the ETV prophylactic group versus 8%, 11.2%, and 25.9% (P = .019)

Lau G. Gastroenterology. 2003. Hsu C. Hepatology. 2008. Huang Y. J Clin Oncol. 2013.

Prophylaxis > pre-emptive therapy

Duration of therapy and monitoring

Loomba R. Gastroenterology. 2017. Hwang J. J Oncol Pract. 2015. Pattullo V. Clin Mol Hepatol. 2016.

Guideline Duration Monitoring

AGA 2-4 weeks prior to initiation and 6-12 months after last dose LFTs and HBsAg levels: every 3 months until 6 months after last dose EASL Receiving Rituxan: at least 18 months after cessation of therapy Immunosuppressive therapy: at least 12 months During prophylaxis: LFTs and HBV DNA every 3 to 6 months After withdrawal: LFT and HBV DNA at least 12 months after ASCO Up to 12 months after cessation of therapy HBV DNA and ALT levels every 3 months during therapy

AGA: American Gastroenterological Association, EASL: European Association for the Study of the Liver is a European, ASCO: American Society of Clinical Oncology

Conclusions

¡ Prophylaxis treatment with nucleotide analogs is

recommended in patients with moderate or high risk of HBVr

¡ Institution screening tools should include HBsAg, anti-HBc,

and HBV DNA to assess the risk of reactivation prior to the initiation of Rituxan

Thank You