9/26/2016
1
Jacob Hobbs, PharmD, BCOP
September 30, 2016
Cancer Immunology: Release the Beast
Disclosure I have no actual or potential conflict of interest in
relation to this presentation
Objectives Describe the mechanism of action of oncologic
immunotherapy agents
Identify the current indications for immunotherapy and the associated data
Summarize the unique toxicities of immunotherapy and recommended treatment strategies
9/26/2016
2
Immunity
Accessed from Nature Reviews Cancer 4, 11-22
Tumor Immunology
Tumor
N
N
N
N
NN
TumorAntigen
DendriticCell
N
N
Resting T Cells
NN
I
I
I
I
Cytokine releaseT Cell attraction
Lymph Node
(Go Hawks!)
Activated T Cell
Priming Phase(Lymph node)
Dendritic cellT cell
MHC TCR
B7
CD28
CTLA-4
DendriticCell
T Cell
MHCTCR
B7
B7
CTLA-4
CD28
Antigen
Activation Signal
Inhibition Signal
Ribas A. N Engl J Med. 2012;366:2517-2519.
N
N
9/26/2016
3
CTLA-4 Inhibition
Dendritic cellT cell
MHC TCR
B7
CD28
CTLA-4
DendriticCell
T Cell
MHCTCR
B7
B7
CTLA-4
CD28
Antigen
Activation Signal
Inhibition Signal
Ipilimumab
Ribas A. N Engl J Med. 2012;366:2517-2519.
N
N
Kill Phase(Peripheral Tissue)
Tumor cellT cell
MHCTCR
B7
CD28
CTLA-4
T Cell
MHCTCR
Inhibition Signal
PD-1PDL-1
Tumor Cell
Ribas A. N Engl J Med. 2012;366:2517-2519.
Tumor
PD-1/PD-L1 Inhibition
Tumor cellT cell
MHCTCR
B7
CD28
CTLA-4
T Cell
MHC TCR
Atezolizumab
PD-1PD-L1
Tumor
PembrolizumabNivolumab
Ribas A. N Engl J Med. 2012;366:2517-2519.
9/26/2016
4
FDA Approved Checkpoint Inhibitors
Ipilimumab(Yervoy)
• CTLA-4 inhibitor• 2011• Unresectable or
metastatic melanoma
• Adjuvant melanoma
Pembrolizumab(Keytruda)
• PD-1 inhibitor• 2014• Unresectable or
metastatic melanoma
• Metastatic NSCLC (PDL-1+)
• Metastatic Head and Neck
Nivolumab(Opdivo)
• PD-1 inhibitor• 2014• Unresectable or
metastatic melanoma
• Metastatic NSCLC
• Renal Cell• Hodgkin
Lymphoma
Atezolizumab
(Tecentriq)
• PD-L1 inhibitor• 2016• Metastatic
bladder cancer
Ipilimumab
Unresectable or metastatic melanoma 3 mg/kg IV every 3 weeks x
4 doses
Median OS of 10.1 mos vs 6.4 mos with gp100 [1]
FDA approved 2011
Hodi FS, et al. N Engl J Med. 2010;363:711-723. For educational purposes only
9/26/2016
5
Ipilimumab Adjuvant treatment of melanoma
10 mg/kg IV q3 weeks x 4 doses; followed by 10 mg/kg IV q12 weeks for up to 3 yrs
Approval based on median RFS 26 mos vs 17 mos with placebo[1]
Median survival not reached in either arm
52% discontinued treatment due to side effects – 5 died
In combination with nivolumab for BRAF V600 wild type, unresectable or metastatic melanoma (first line) Dosing guideline: ipilimumab 3 mg/kg IV q3w x 4 + nivolumab 1
mg/kg IV q3w x 4, then nivolumab monotherapy
PFS 11.5 months (combo), 6.9 months (nivo), 2.9 months (ipi)
ORR 57.6% (combo), 43.7% (nivo), 19% (ipi) [2]
Approval based on 61% ORR with combination vs 11% with ipilimumab monotherapy[3]
1)Eggermont AM, et al. Lancet Oncol. 2015;16:522-5302)Larkin J, et al. N Engl J Med. 2015;373:23-343)Postow MA, et al. N Engl J Med. 2015;372:2006-2017
Nivolumab Unresectable or Metastatic Melanoma (front line +/-
ipilimumab, or beyond) 240 mg IV q 2 weeks
Metastatic NSCLC (2nd line or beyond) Squamous: median OS 9.2 vs 6.0 mos with docetaxel [1]
Nonsquamous: OS 12.2 vs 9.4 mos docetaxel. Median PFS favored docetaxel 4.2 vs 2.3 months but rate of PFS at 1 year higher with nivolumab 19% vs 8%[2]
Advanced RCC (following antiangiogenic therapy) Median OS 25.0 vs 19.6 months vs everolimus[3]
ORR 25% vs 5%, median PFS not significant Classical Hodgkin’s Lymphoma (following relapse or
progression after stem cell transplant and brentuximabvedotin 3 mg/kg IV q 2 weeks 23 patients - ORR 87%; PR 70%, CR 17%[4]
1) Rounds A, et al. Am J Health Syst Pharm. 2015;72:1851-1855. 2) Borghaei H, et al. N Engl J Med. 2015;373:1627-1639. 3)Motzer RJ, et al. N Engl J Med. 2015;373:1803-1813. 4)US Food and Drug Administration. Nivolumab (Opdivo) for Hodgkin Lymphoma. www.fda.gov
Pembrolizumab Unresectable or metastatic melanoma (first line or beyond) [1]
2 mg/kg IV q 3 week
ORR vs ipilimumab: 34% vs 12%, in previously untreated pts
Improved PFS and OS vs ipilimumab, less Grade 3-5 toxicity
Metastatic NSCLC (PD-L1+ with approved test) after first-line therapy[2]
Median OS all patients: 10.4 months vs 8.5 months on docetaxel, PFS non significant
OS for Patients with at least 50% PD-L1 expression: 14.9 months vs 8.2 months, PFS 5 months vs 4.1 months
Head and neck cancer, squamous cell, recurrent or metastatic after platinum-containing chemotherapy[3]
200 mg IV q 3 week until progression, toxicity, or up to 24 months
ORR 16%, 82% of responders had responses of 6 months or longer
1)Robert C, et al. N Engl J Med. 2015;372:2521-25322)Herbst RS, et al. Lancet. Published online Dec 12, 20153)US Food and Drug Administration. Pembrolizumab for head and neck cancer. www.fda.gov
9/26/2016
6
Atezolizumab Locally advanced or metastatic urothelial carcinoma with
progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant/adjuvant treatment with platinum-containing chemotherapy 1200 mg IV q 3 week
ORR 14.8% Patients with > 5% expression of PD-L1 in tumor-infiltrating immune cells: ORR
26.0%
Patients with ≤ 5% expression of PD-L1 in tumor-infiltrating immune cells: ORR 9.5%
At median follow up of 11.7 months, 84% of responders had ongoing response
Rosenberg JE, et al. Lancet 2016;387:1909-20
Summary
Metastatic Melanoma Metastatic Non Small Cell Lung Cancer
All > traditional chemo
Pembrolizumab > Ipilimumab
Nivolumab > Ipilimumab
Nivolumab + Ipilimumab > Ipilimumab
Pembrolizumab vs Nivolumab??
2nd line Pembrolizumab > Docetaxel(PD-L1 +)
2nd line Nivolumab > Docetaxel
Nivolumab vs Pembrolizumab??
1st line – Pembrolizumab?
Toxicities of Checkpoint Inhibitors
9/26/2016
7
General Toxicities Common Side Effects Fatigue Cough Nausea Decreased appetite Rash Itching
Less Common Immune related adverse-events
American Cancer Society. www.cancer.org
Grade 3 and 4 ToxicityEvent Nivolumab Nivo + Ipi Ipilimumab
Tx-related AE 16.3% 55% 27.3%
Diarrhea 2.2% 9.3% 6.1%
Fatigue 1.3% 4.2% 1%
Pruritis 0 1.9% 0.3%
Rash 0.6% 4.8% 1.9%
Vomiting 0.3% 2.6% 0.3%
Increased LFT 1.3% 8.3% 1.6%
Colitis 0.6% 7.7% 8.7%
Tx-related AE leading to DC
7.7% 36.4% 14.8%
Larkin, J et al. N Engl J Med 2015;373:23-34
If not vigilant, may result in more serious immune-related AEs
Pulmonary Pneumonitis Interstitial lung
disease Acute interstitial
pneumonitis
Neurologic Autoimmune neuropathy Demyelinating
Polyneuropathy Guillain-Barre Myasthenia gravis–like
syndrome
Hepatic Hepatitis,
autoimmune
Gastrointestinal Colitis Enterocolitis Necrotizing colitis GI perforation
Eye Uveitis Iritis
Renal Nephritis,
autoimmune Renal failure
Skin Dermatitis exfoliative Erythema multiforme Stevens-Johnson
syndrome Toxic epidermal necrolysis Vitiligo Alopecia
Immune-Related AEs With Immunotherapy
Slide credit: clinicaloptions.com
Endocrine Hypothyroidism Hyperthyroidism Adrenal
insufficiency Hypophysitis
9/26/2016
8
Side Effect Time Frame - ipilimumabRash, pruritusLiver toxicityDiarrhea, colitisHypophysitis
Toxi
city
Gra
de
Wks
140 2 4 6 8 10 12
Weber JS, et al. J Clin Oncol. 2012;30:2691-2697. For educational purposes only
Corticosteroid treatment Optimal management based on clinical experience, no
prospective trials to evaluate best treatment strategy Prednisone 1 to 2 mg/kg daily or equivalent
When ≤ grade 1, taper over at least 4 weeks Half life
27 days for PD-1/PD-L1 15.4 days for ipilimumab
Temporary immunosupression does not seem to limit efficacy
Consider Pneumocystis carinii pneumonia prophylaxis in patients requiring ≥ 20 mg of prednisone or equivalent daily for ≥ 4 weeks
PPI or H2 blocker for gastritis Control blood sugars in diabetics
Naidoo J, et al. Annals of Oncology 2015(26)2375-2391
Dermatologic Most common immune related adverse event Usually seen after second cycle, can appear
within first 2 weeks Usually located across limbs and trunk Maculopapular, papulopustular, Sweet’s
syndrome, follicular or urticarial dermatitis, pruritis Rarely lichenoid dermatitis, bullous pemphigoid Vitiligo More common with PD-1 inhibitors in melanoma No cure, might be associated with favorable
outcomes
Naidoo J, et al. Annals of Oncology 2015(26)2375-2391Friedman, CF, et al. JAMA Oncology. Online June 30, 2016
9/26/2016
9
Maculopapular rash
Maculopapular rash
Dermatologic Management Grade 1 (covers <10% of BSA) and 2 (10-30% of BSA)
Can continue treatment, use supportive care Topical corticosteroids – medium to high potency Pruritis – antihistamines, cold compress, oatmeal baths, oral
or topical doxepin, oral aprepitant
Grade 3 or higher (>30% of BSA, blistering, peeling) Hold dose and start prednisone 1 mg/kg/day or equivalent Can restart when grade 1 or lower If no response within 48 hours consider additional
immunosuppression with infliximab, mycophenolate mofetil, or cyclophosphamide
Discontinue if symptoms don’t improve after 12 weeks of supportive care
Naidoo J, et al. Annals of Oncology 2015(26)2375-2391Friedman, CF, et al. JAMA Oncology. Online June 30, 2016
9/26/2016
10
Dermatologic management Rare cases of Stevens-Johnson syndrome/toxic
epidermal necrolysis Hospitalize with IV fluids and electrolyte
replacement Prednisone 1-2 mg/kg/day or methylprednisolone 1-
4 mg/kg/day IV Discontinue treatment
Mucositis, gingivitis, sicca syndrome Steroid oral rinses, viscous lidocaine, good oral
hygiene
Naidoo J, et al. Annals of Oncology 2015(26)2375-2391Friedman, CF, et al. JAMA Oncology. Online June 30, 2016
Diarrhea/Colitis Median time to onset – 6 to 8 weeks after
initiation
Important to distinguish diarrhea from colitis
Colitis-related mortality delayed reporting, noncompliance, and not withholding treatment
Nothing known to prevent immune-related diarrhea
Developing colitis with ipilimumab does not prohibit use of PD-1 inhibitors
Naidoo J, et al. Annals of Oncology 2015(26)2375-2391Friedman, CF, et al. JAMA Oncology. Online June 30, 2016
Diarrhea/Colitis Management Minimal increase in bowel movements over
baseline Loperamide, atropine, diphenoxylate and atropine Oral budesonide 9 mg daily
Symptoms persist more than 3 days or worsen Rule out infectious cause Hold therapy Oral prednisone 1 to 2 mg/kg/day or IV methylprednisolone
2mg/kg twice daily Get endoscopic or radiologic evaluation to confirm diagnosis
Symptoms don’t improve on corticosteroids Add infliximab 5 mg/kg once every 2 weeks until controlled Colonoscopy not needed unless diagnosis is unclear
Naidoo J, et al. Annals of Oncology 2015(26)2375-2391Friedman, CF, et al. JAMA Oncology. Online June 30, 2016
9/26/2016
11
Hepatitis Commonly 8 to 12 weeks after starting treatment
Most cases are asymptomatic
AST/ALT elevations more common than total bilirubin
No characteristic radiographic finding noted, hepatomegaly or periportal edema in severe cases
Monitor liver function before every dose
Rule out viral or other drug induced hepatitis
Consider radiologic evaluation to exclude malignancy
Median time to resolution 8 weeks
Naidoo J, et al. Annals of Oncology 2015(26)2375-2391Friedman, CF, et al. JAMA Oncology. Online June 30, 2016
Hepatitis Management
Grade Treatment Follow-up
1AsymptomaticAST/ALT ≤ 2.5 x ULNT Bilirubin ≤ 1.5 x ULN
•Continue therapy if asymptomatic•Monitor LFT routinely until resolved
•If LFTs worsen or patient develops symptoms, treat as higher grade
2AST/ALT 2.6-5 x ULNT Bilirubin 1.6-3 x ULN
•Hold therapy•Oral prednisone 0.5 - 1 mg/kg/day or equivalent•Monitor LFT daily
•After symptoms improve, taper steroids ≥1 month with weekly LFT•Resume once ≤ grade 1
3 - 4AST/ALT > 5 x ULNT Bilirubin > 3 x ULN
•Discontinue immunotherapy•IV prednisolone 2-4 mg/kg/day or equivalent•Monitor LFT daily•If no improvement in 3 days, add mycophenolate mofetil 500-1000mg every 12 hours or tacrolimus•*Do not add infliximab*
•After symptoms and LFT improve, taper steroids ≥ 1 month with weekly LFT•Could add antithymocyte globulin 1.5 mg/kg for 2 consecutive days if no response•Patients may have a rebound in LFT elevations
Naidoo J, et al. Annals of Oncology 2015(26)2375-2391Friedman, CF, et al. JAMA Oncology. Online June 30, 2016
Pneumonitis More common in lung and renal cell carcinoma
Occurs later, 7.4 – 24.3 months after starting
Can be fatal if not treated appropriately
Check CT scan for shortness of breath, cough, fever, chest pain, or hypoxia
Naidoo J, et al. Annals of Oncology 2015(26)2375-2391Friedman, CF, et al. JAMA Oncology. Online June 30, 2016Nishino M, et al. JAMA Oncology. Online August 18, 2016
9/26/2016
12
Pneumonitis Management
Grade Treatment Follow-up
1AsymptomaticRadiologic changes only
•Continue therapy•Monitor for symptoms every 3 days
•Repeat CT chest scan every cycle•If symptoms develop, treat as higher grade
2Mild to moderate new symptoms
•Hold therapy•Oral prednisone 1 mg/kg/day or equivalent•Monitor for symptoms daily
•If improve to ≤ grade 1 within 3 days of supportive care, resume therapy at next dose•If persistent after 3 days, discontinue therapy•After symptoms improve, taper steroids ≥1 month
3 - 4Severe or life-threatening new symptomsWorsening hypoxia
•Discontinue immunotherapy•Hospitalization•Consider pulmonary/infectious disease consults and bronchoscopy•IV prednisolone 2-4 mg/kg/day or equivalent•Prophylactic antibiotics
•After symptoms improve to ≤ grade 1 or baseline, taper steroids ≥ 6 weeks•If worsens in 48 hours consider adding infliximab, cyclophosphamide, or mycophenolate mofetil
Naidoo J, et al. Annals of Oncology 2015(26)2375-2391Friedman, CF, et al. JAMA Oncology. Online June 30, 2016
Endocrine Toxicities Incidence difficult to assess due to variable
methods of assessment in clinical trials
Hypophysitis and hypothyroidism most common
Rare hyperthyroidism, thyroiditis, adrenal insufficiency, and insulin-dependent diabetes
Difficult to diagnose – headache, fatigue, nausea, depression
Naidoo J, et al. Annals of Oncology 2015(26)2375-2391Friedman, CF, et al. JAMA Oncology. Online June 30, 2016
Hypophysitis Management Fatigue, headache, hypogonadism, hypotension,
hypoglycemia
Enlargement of pituitary gland
All or some of the pituitary hormones can be reduced (ACTH, THS, FSH, LH, growth hormone, prolactin)
Symptomatic - prednisone 1 mg/kg/day or equivalent
Hydrocortisone 20 mg every morning and 10 mg every evening for hypoaldrenalism
Naidoo J, et al. Annals of Oncology 2015(26)2375-2391Friedman, CF, et al. JAMA Oncology. Online June 30, 2016
9/26/2016
13
Thyroid Management Usually seen after 2 to 4 infusions of ipilimumab, variable
with PD-1/PD-L1 inhibitors Check thyroid function at baseline Recommended before every dose of ipilimumab,
periodically with PD-1/PD-L1 inhibitors Primary hypothyroidism (low free T4 and high TSH) –
thyroid hormone replacement and can continue immunotherapy
Secondary hypothyroidism from hypophysitis (low free T4 and low TSH) – thyroid hormone replacement and hydrocortisone
Hyperthyroidism – standard antithyroid pharmacotherapy Thyroiditis – beta blockers in symptomatic cases
Naidoo J, et al. Annals of Oncology 2015(26)2375-2391Friedman, CF, et al. JAMA Oncology. Online June 30, 2016
Andrenal Insufficiency Management Can rarely cause adrenal crisis – dehydration,
hypotension, hyperkalemia, hyponatremia Hospitalize and hydrate aggressively Consult endocrinology Stress dose IV corticosteroids Long term hydrocortisone supplementation likely Consider increased doses during medically stressful
situations Surgery Infection
Evaluate clinical situation before restarting immunotherapy
Naidoo J, et al. Annals of Oncology 2015(26)2375-2391Friedman, CF, et al. JAMA Oncology. Online June 30, 2016
Less Common Toxicity Pancreatitis
Treat with corticosteroids if all other causes excluded If elevated amylase and/or lipase but no symptoms or
inflammation shown on scans – do not need to start steroids Uveitis, episcleritis, conjunctivitis
Consult ophthalmologist Topical intraocular corticosteroids – prednisolone 1 %
suspension Oral corticosteroids with grade 3 or 4, or refractory cases
Nephritis Several reports with ipilimumab monotherapy and in
combination with nivolumab Oral or IV corticosteroids Discontinue therapy if grade 3 or 4
Naidoo J, et al. Annals of Oncology 2015(26)2375-2391Friedman, CF, et al. JAMA Oncology. Online June 30, 2016
9/26/2016
14
Less Common Toxicity
• Neuropathy, aseptic meningitis, temporal arteritis, myasthenia gravis-like syndrome, posterior reversible encephalopathy syndrome, Guillain-Barre syndrome
• IV methylprednisolone 2 mg/kg/day• Plasmapheresis and IV immunoglobulin• Grade 3 or 4 permanently discontinue
Neurologic
• Red cell aplasia, neutropenia, acquire hemophilia A
• Corticosteroids• Bone marrow biopsy if diagnosis remains
unclearHematologic
Naidoo J, et al. Annals of Oncology 2015(26)2375-2391Friedman, CF, et al. JAMA Oncology. Online June 30, 2016
Side effect management summary Any grade 1 or isolated hypothyroidism – symptom
management and continue treatment
Grade 2 pneumonitis, nephritis, hepatitis, symptomatic hypophysitis, and all other grade 3 AE Hold treatment, start steroids
Grade 3 or 4 pneumonitis, nephritis, hepatitis, infusion-related reaction, any other grade 4 reaction, any recurrent grade 3 AE, no improvement to ≤ grade 1 or cannot taper steroids to ≤ 10 mg/day of prednisone or equivalent within 12 weeks Permanently discontinue
Common Checkpoint Inhibitor Questions
9/26/2016
15
Why did nivolumab’s dose change? Attempt to reduce dosing errors and wait time 80 kg was the approximate median body weight in clinical trials – 80 kg
x 3 mg/kg = 240 mg Model-based simulation to evaluate predicted exposure
Data derived from an integrated population pharmacokinetic analysis dataset with data from patients in 9 nivolumab trials
Range of predicted exposure with 240 mg overlapped with 3 mg/kg dosing for a wide range of body weights Median % difference in geometric means in systemic exposure
~5% melanoma and NSCLC ~3% renal cell carcinoma
Weight range 35 – 168 kg Dose/exposure response appears to be flat
Difference in dose not likely to affect efficacy and safety Hodgkin Lymphoma – 3 mg/kg IV q 2 weeks Melanoma in combination with ipilimumab – 1 mg/kg IV q 3 weeks x 4
doses, then 240mg
Data to File. NIVO 166. Bristol-Myers Squibb Company, Princeton, NJData to File. NIVO 170. Bristol-Myers Squibb Company, Princeton, NJ
What is pseudoprogression?
Screening Wk 8: “Progression” Wk 12: Improvement
Wk 16: Continued Improvement
Wk 72: CR Wk 108: Continued CR
Ribas A, et al. Clin Cancer Res. 2009;15:7116-7118.
Response to ipilimumab
Slide credit: clinicaloptions.com
Should we test for PD-L1 expression? Mixed results with response to checkpoint
inhibitors
Only FDA indication that requires testing is pembrolizumab use in non small cell lung cancer
Different cut off levels used for positivity
Different tests used for each drug
Expression can vary among primary and metastatic sites
PD-1 expression can change through time and treatment
Shien K, et al. Lung Cancer. 2016;99:79-87
9/26/2016
16
Shien K, et al. Lung Cancer. 2016;99:79-87
Can I use it in my patient with an autoimmune condition? Excluded from clinical trials Johnson DB, et al JAMA Oncol 2016;2(2):234-240
Retrospective review of 30 patients who had preexisting autoimmune disorders who received ipilimumab for melanoma
Rheumatoid arthritis, psoriasis, inflammatory bowel disease, lupus, multiple sclerosis, thyroiditis
43% were on immunosuppression during treatment 27% exacerbated autoimmune condition requiring treatment 10 patients developed Grade 3 – 5 autoimmune AE – 2 cases were
reversible 50% had no flare in underlying autoimmune disease or AE 20% objective response, 1 durable complete response 1 death from immune related colitis – psoriasis patient
Use clinical judgment, discuss risks with patient
My patient is responding to therapy but had a serious adverse event. Should I rechallenge?
Same adverse event or new severe effects may arise Monitor very closely 53 yo male with metastatic melanoma
Grade 3 colitis after 3 cycles of ipilimumab Resolved with high dose corticosteroids
Also developed hypophysitis Required thyroid and steroid replacement
Later developed grade 3 arthralgia on nivolumab High dose corticosteroids, followed by sulfasalazine and
hydroxychloroquine
6 months later tried pembrolizumab Admitted for liver failure 11 days after first dose, died within 3
days
Ludlow SP, et al. Melanoma Research 2016,26:316-318
9/26/2016
17
Use with low dose corticosteroids? No known drug – drug interactions
Patients receiving immunosuppressants excluded from trials
Corticosteroids suppress T cells
Would likely blunt drug efficacy but to what extent?
Use in pregnancy/breastfeeding? No during therapy and for at least 3 months after stopping
ipilimumab, 4 months for pembrolizumab, 5 months for nivolumab and atezolizumab
Keytruda (package insert). Merck. Accessed online September 8, 2016Opdivo (package insert). Bristol-Myers Squibb. Accessed online September 8, 2016Yervoy (package insert). Bristol-Myers Squibb. Accessed online September 8, 2016Tecentriq (package insert). Genentech. Accessed online September 8, 2016
Are checkpoint inhibitors expensive?
Tartari F, et a. Cancer Treat Rev. 2016;48:20-4Image from alivecampus.com
What is next? Figuring out who would benefit most
Combination with other immunotherapy, chemotherapy, targeted agents
Find tangible biomarkers to help predict response
Understand the optimal dosing and duration of treatment
Improve the management of toxicities
9/26/2016
18
Questions 1) Patient KG is starting nivolumab for metastatic melanoma.
Which of the following items should be monitored regularly during treatment?A. Blood pressureB. EKGC. Liver function testsD. Blood glucose
2) KG later develops grade 3 diarrhea after several months of therapy. What is the most appropriate treatment recommendation?A. Resume therapy and start loperamide 2 mg every 2 hours as neededB. Hold therapy and start loperamide 2 mg every 2 hours as neededC. Hold therapy and start a 6 day methylprednisolone taper dose packD. Hold therapy and start prednisone 1 to 2 mg/kg daily tapered over
several weeks
Questions?