Immunotherapy and Checkpoint Inhibitors Flashcards
Cancer cells express ____ to bind to ____ and turn off immune T-cells in our immune response.
Choose between PD-1 and PD-L1
PD-L1 is on the tumor cell; PD-1 is on the T-cell
Ipilimumab is what kind of immune checkpoint inhibitor drug?
A) PD-1 inhibitor
B) PD-L1 inhibitor
C) CTLA4 inhibitor
C) CTLA4 inhibitor
Pembrolizumab is what kind of immune checkpoint inhibitor?
A) anti-PD-L1
B) anti-PD-1
C) anti-CTLA4
B) anti-PD-1
Immunotherapies have equal therapeutic effect in all cancers. True or False?
False. Each type of cancer has a different degree of mutation proteins. Ones with more mutated proteins represents more potential targets for immune recognition and destruction (i.e. melanoma, lung cancer)
Which ones are in the same class and name that class? Ipilimumab Nivolumab Durvalumab Atezolizumab Pembrolizumab Avelumab
PD-1: Pembrolizumab, Nivolumab
CTLA4: Ipilimumab
PD-L1: Atezolizumab, Durvalumab, Avelumab
In terms of drug-drug interactions, what is the most important one to know amongst checkpoint inhibitors? A) Allopurinol B) CYP3A4 inhibitors/inducers C) NSAIDs D) No significant drug-drug interations
D) No significant drug-drug interations
Which of the following blocks inhibitory signal that lets cancer survive through CTLA4? A) Nivolumab B) Pembrolizumab C) Ipilimumab D) Avelumab
C) Ipilimumab
Tumors often have mutations that cause impaired DNA mismatch repair, allowing the tumor to generate many mutant proteins that could serve as tumor antigens, triggering an immune response against the tumor. True or False?
True
Pembrolizumab MOA is described in all EXCEPT:
A) By preventing the self-checkpoint system from blocking the T-cells
B) Blocking our own PD-1 from binding to tumor cell PD-L1
C) Release the “brake” allowing T-cell to act
D) Blocking our CTLA-4 to prevent cancer from binding
D) Blocking our CTLA-4 to prevent cancer from binding
Which of the following can be used in combination with Nivolumab? A) Pembrolizumab B) Atezolizumab C) Ipilimumab D) Durvalumab
C) Ipilimumab (CTLA 4 inhibitor)
Immune checkpoint inhibitors have consequences of an overly active immune system. What do we call these?
Immune-related adverse events (irAEs)
Onset of irAEs can be (select all that apply)
A) immediate
B) delayed
C) affect any organ system
D) are a result of immune activation and inflammation
A) immediate
B) delayed [as much as 2 years]
C) affect any organ system
D) are a result of immune activation and inflammation
How do you manage irAEs of immune checkpoint inhibitors?
A) premeds
B) early symptom recognition and prompt intervention
C) hold drug
D) treat with corticosteroids and symptom management
B) early symptom recognition and prompt intervention
D) treat with corticosteroids and symptom management
What is the order of irAEs with immune checkpoint inhibitors?
A) diarrhea, colitis –> rash, pruritus –> liver tox + endocrine imbalance
B) rash, pruritus–> diarrhea, colitis –> liver tox + endocrine imbalance
C) liver tox + endocrine imbalance –> diarrhea, colitis –> rash, pruritus
D) diarrhea, colitis –> liver tox + endocrine imbalance –> rash, pruritus
B) rash, pruritus (3 weeks) –> diarrhea, colitis (5 weeks) –> liver tox + endocrine imbalance (7 weeks)
What is the most common irAE? A) Fatigue B) Diarrhea, colitis C) Hepatitis C) Maculopapular rash
C) Maculopapular rash
How do you manage maculopapular rash from immune checkpoint inhibitors? A) Keratolytic cream B) Steroid cream/gel C) Oral antihistamine D) Discontinuation of therapy
All of these are based off severity
B) Steroid cream/gel
C) Oral antihistamine
D) Discontinuation of therapy [severe AE]
Fatigue is common treatment with checkpoint inhibitors, but it could mean which of the other irAEs? A) Hepatitis B) Adrenal insufficiency C) Colitis D) Diarrhea
B) Adrenal insufficiency (hormone-related problems)
Of the GI irAEs, what is the most common with colitis and what is usually asymptomatic? A) Constipation; Hepatitis B) Diarrhea; Colitis C) Diarrhea; Hepatitis D) Constipation; Colitis
C) Diarrhea; Hepatitis
Mild symptoms of GI irAEs includes 1-3 BMs above normal per day. What would be good treatment options? A) Loperamide (Imodium) B) Diphenoxylate/atropine (Lomotil) C) Hold therapy D) Self-limiting
A) Loperamide (Imodium)
B) Diphenoxylate/atropine (Lomotil)
How many BM above normal is considered severe GI irAEs? A) 1-3 B) 4-6 C) 6+ D) Constant
C) 6+
What are signs of hepatitis in terms of labs?
elevations AST/ALT (transaminitis) + elevation of bilirubin
Immune checkpoint inhibitor therapy can adversely affect the body’s hormone-producing organs and glands (endocrine system). True or False?
True
What kind of labs would be drawn if endocrine system was attacked? A) Thyroid levels B) Blood glucose C) Cortisol D) Aldosterone
A) Thyroid levels
B) Blood glucose
C) Cortisol & D) Aldosterone – Addison’s disease
What are other less common areas that can be attacked due to overreactive immune system? A) Lungs B) Brain C) Heart D) Eyes E) Kidneys
A) Lungs - pneumonitis
B) Brain - neurologic are rare but very serious (can attack spinal cord too)
C) Heart - myocarditis, pericarditis, arrhythmias, impaired LVEF
D) Eyes - dry eyes, uveitis
E) Kidneys - kidney failure
+ acute pancreatitis
MOA of IMiDs (Thalidomide, Lenalidomide, Pomalidomide)
A) Stimulates immunomodulatory properties
B) Inhibits cell proliferation and induces apoptosis of tumor cells
C) Inhibits angiogenesis (VEGF, TNF-alpha, IL-6)
D) All of the above
A) Stimulates immunomodulatory properties
B) Inhibits cell proliferation and induces apoptosis of tumor cells
C) Inhibits angiogenesis (VEGF, TNF-alpha, IL-6)
D) All of the above
Indication for IMiDs (Thalidomide, Lenalidomide, Pomalidomide)
Multiple Myeloma
IMiDs (Thalidomide, Lenalidomide, Pomalidomide) ROA
All oral agents
Unique about IMiDs (Thalidomide, Lenalidomide, Pomalidomide)
FDA requires enrollment in REMS due to teratogenicity
Warnings and ADRs with IMiDs (Thalidomide, Lenalidomide, Pomalidomide)
Teratogenic (need 2 forms on contraception)
VTE (use baby ASA as anticoag ppx), Constipation, rash
Peripheral neuropathy & Sedation (Thalidomide)
Myelosuppression (Lenalidomide and Pomalidomide)
What are the vaccines for immunotherapy? A) T-VEC B) IL-2 C) Sipuleucel-T D) TIL
A) T-VEC
C) Sipuleucel-T
T-VEC (Talimogene) is described by which of the following (select all that apply):
A) Genetically modified herpes simplex virus 1
B) Oncolytic viral therapy designed to replicate in melanoma cells
C) Live attenuated
D) CI for infection and pregnant women
A) Genetically modified herpes simplex virus 1
B) Oncolytic viral therapy designed to replicate in melanoma cells
C) Live attenuated
D) CI for infection and pregnant women
Which cytokines are involved in cytokine therapy? A) IL-6 B) IL-2 C) TNF-alpha D) IFN-alpha
B) IL-2
D) IFN-alpha
Why have cytokine therapy fallen out of favor?
Substantial toxicities + introduction of more targeted immune therapy (checkpoint inhibitors)
One of the first immunotherapies that demonstrate clinical efficacy in cancer tx
Augments immune function by promoting the growth and activity of T cells and NK cells
Should restrict to those with normal cardiac and pulmonary function. Must be administered inpatient. Describes which cytokine therapy?
IL-2
Induces expression of many genes, inhibits protein synthesis and exerts a number of different effects on diverse cellular processes
Not curative, but can induce partial responses in follicular lymphoma, hairy cell lymphoma, CML, and melonoma
INF-alpha
Main ADRs to think of with IL-2
Capillary leak syndrome: hypotension, dyspnea, renal dysfunction, metabolic acidosis, edema
Main ADRs to think of with INF-alpha
Autoimmune reaction: thyroid dysfunction, psoriasis
Neurologic: flu-like syndrome, fatigue, confusion, depression
What are immune checkpoints?
A) Checkpoint pathways allow the immune cells to evaluate the attack against the threat at multiple stages
B) Crucial for maintaining immune tolerance to “self antigens”
C) Modulates the length and magnitude of immune response of effectors in different tissues to try to minimize the tissue damage
D) Cancer cells have adopted immunosuppressive pathways to bypass these immune checkpoints and shut down the activation of immune cells
Checkpoint inhibitors dosing and frequency is A) based on indication B) weight-based C) flat dosing D) titration dosing
A) based on indication
C) flat dosing
What should you avoid because checkpoint inhibitors are immune-mediated reactions?
Steroids unless treating immune-related toxicity
**no DDIs since doesn’t go through CYP
How to manage checkpoint inhibitors toxicities A) Steroids B) Dose reduction C) Interrupt therapy permanently D) Interrupt therapy temporarily
B) Dose reduction
C) Interrupt therapy permanently
D) Interrupt therapy temporarily
**steroids only used for treating immune-related toxicities
What is required for T-cell activation?
1) MHC with antigen binding to the T-cell receptor
2) Co-stimulatory signal B-7 on the APC binding to CD28 on the T cells
CTLA-4 is a ____ regulator of T-cell activation.
Positive or negative?
Negative
If CTLA-4 (CD28) is present and binds to B-7 on the APC, a signal to shut down is sent to the T-cell
What do you do if hepatotoxicity or renal toxicity during treatment of Ipilimumab (Yervoy)?
Consider holding or permanently discontinuing
Monitoring for anti-CTLA-4 (Ipilimumab - Yervoy)
Hepatic (ALT, AST, T bili)
Renal (Scr)
Thyroid function
S/xs of immune-mediated adverse reaction
Non-immune mediated adverse effects of Ipilimumab
Fatigue (potential hormone imbalance), nausea, vomiting, HA, weight loss, pyrexia, decreased appetite, insomnia
PD-L1 on the tumor cell can bind to PD-1 on T-cell, leading to inactivation of the T-cell, allowing the tumor cells to evade immune response. True or false?
True
Which PD-1 inhibitor do you need to monitor electrolytes for? A) Pembrolizumab B) Nivolumab C) Cemiplimab D) none of these
B) Nivolumab: hyponatremia, hypomagnesemia, hypokalemia OR hyperkalemia, hypercalcemia
Which PD-L1 inhibitors has a high risk infusion related reaction? A) Atezolizumab B) Durvalumab C) Avelumab D) none of these
C) Avelumab (needs premeds: antihistamine, APAP)
Which of the following irAEs are potentially irreversible?
Endocrinopathy
What are the most common irAEs?
In the skin (first one; within 3-4 weeks) and GI tract (colitis)
When do you need to hold immunotherapy and permanently d/c for immune-related dermatologic adverse effects (pruritus, maculopapular rash)?
A) Mild
B) Moderate
C) Severe
B) Moderate (affects QOL) - hold, resume when symptoms resolve
C) Severe (not manageable with prior interventions and intolerable) - permanent
Pharmacologic management of immune-related dermatologic adverse event
Mild: give emollient or cream
Mod: hold, topical emollient and high topical corticosteroids, prednisone if no resolution. slowly taper (over 4-6 weeks) when resolved
Severe: permanently d/c, methylprednisolone 1-2 mg/kg, slowly taper when resolved
What irAEs occurs at the onset of 5-8 weeks?
Diarrhea (most common), abdominal pain, colitis
Management of immune-related colitis adverse event
Mild (<4 stools over baseline): give loperamide
Mod (4-6): hold, start antidiarrheal, steroid if no resolution, resume
Severe (>=7): permanently d/c, methylpred, infliximab (remicade) if refractory after 2-3 days
What irAEs occurs at the onset of 6-8 weeks?
Endocrine
What are things to monitor with immune-related endocrine adverse event?
ACTH
Thyroid function (TSH and T4)
Blood glucose
Testosterone
Management of immune-related endocrine adverse event
Correcting endocrine abnormality with steroids and/or hormonal replacement (i.e. levothyroxine, testosterone, etc.)
In severe hypothyroidism, do not need to discontinue agent. Can hold until symptoms resolve to baseline with appropriate supplementation
