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Oncology > Immunotherapy > Flashcards

Immunotherapy Flashcards

1
Q

Why immunotherapy for cancers?

A
  • Specificity
  • Immunological memory
  • Adaptability
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2
Q

Ipilimumab

A
  • Monoclonal antibody
  • CTLA-4 blockade
  • Treats metastatic melanoma
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3
Q

What are the mechanisms of actions of Anti-CTLA-4?

A
  • Hard wired
  • Targets CD28 pathway (T cell activation)
  • Works during priming
  • Expands clonal diversity
  • Primarily effects CD4+ T cells
  • Can move T cells into tumors
  • Disease reoccurence after response is rare
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4
Q

What are the mechanisms of actions of anti-PD-1?

A
  • Induce resistance
  • Targets TCR pathway (signaling pathway)
  • Works during exhausted T cells
  • Does NOT expand clonal diversity
  • Primarily effects CD8+ T cells
  • Does NOT move T cells in tumors
  • Disease reoccurence after response is significant
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5
Q

What is a biomarker of response to anti-PD-1 therapy?

A
  • Tumor mutational burden
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6
Q

What are some hormone gland side effects?

A
  • Persistent or unusual headache
  • Extreme tiredness
  • Weight loss or gain
  • Rapid heartbeat
  • Increased sweating
  • Hair loss
  • Constipation
  • Dizziness or fainting
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7
Q

What are some skin side effects?

A
  • Rashes
  • Itching
  • Blistering
  • Painful sores or ulcers
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8
Q

What are some liver side effects?

A
  • Yellowing of the skin or the whites of the eyes
  • Severe nausea or vomiting
  • Pain on the right side of the stomach area
  • Dark urine
  • Bleeding or bruising more easily than normal
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9
Q

What are some intestinal side effects (colitis)?

A
  • Diarrhea or more bowel movements than usual
  • Stools that have blood or are dark, tarry, or sticky
  • Severe stomach-area pain
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10
Q

What are some side effects of immunotherapy?

A

Most common:
* GI tract
* Endocrine glands
* Skin
* Liver
Less often:
* CNS
* Cardiovascular
* Pulmonary
* Musculoskeletal
* Hematological

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11
Q

How do you diagnose and treat dermatitis?

A
  • Clinical examination, skin biopsy
  • Topical steroids, oral steroids
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12
Q

How do you diagnose and treat endocrinopathy?

A
  • TSH, T4, cortisol, ACTH
  • Hormone replacement
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13
Q

How do you diagnose and treat colitis?

A
  • Clinical, endoscopy
  • Oral steroids
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14
Q

How do you diagnose and treat hepatitis?

A
  • AST, ALT
  • Oral steroids
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15
Q

When do immune-related adverse events occur?

A

First few weeks to months after treatment but can occur anytime, even after treatment discontinuation
* Dermatologic adverse events are usually first to appear

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16
Q

Are immune-related adverse events associated with the efficacy of immune-checkpoint blockade?

A
  • Conflicting data are available
  • The development of immune-related events is not required for treatment benefit
  • Specific adverse events may be more clearly associated with treatment efficacy
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17
Q

Does immunosuppression to treat such adverse events reduce the antitumor efficacy of treatment?

A
  • Beneficial responses can persist despite the use of immunosuppression to treat immune-related events
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18
Q

Is it safe to restart treatment after a major adverse event?

A
  • Retrospective studies have shown that immune-related adverse events associated with one class of agent may not necessarily recur during subsequent treatment with another agent
  • The safety of treatment probably depends on the severity of the initial immune-related adverse event
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19
Q

What are the proposed mechanism of LAG-3?

A
  • Attenuated cytokine secretion
  • Inhibit via signal transduction
  • Enhance the function of Tregs
20
Q

What are the main components of CAR T cell therapy?

A
  • Antigen-recognition
  • Transmembrane
  • Intracellular domain
21
Q

Nivolumab

A
  • Targets PD-1
  • Melanoma, non-small cell lung cancer, Hodgkin’s lymphoma, squamous cell carcinoma, colorectal cancer
22
Q

Pembrolizumab

A
  • Targets PD-1
  • Melanoma, non-small cell lung cancer, Hodgkin’s lymphoma, squamous cell carcinoma, solid tumors with high MSI
23
Q

Dostarlimab

A
  • Targets PD-1
  • Endometrial cancer and solid tumors with mismatch repair deficient (MMR)
24
Q

Cemiplimab

A
  • Targets PD-1
  • Non-small cell lung cancer, basal cell carcinoma, cutaneous squamous cell carcinoma
25
Q

Atezolizumab

A

Non-small cell lung cancer, urothelial carcinoma

26
Q

Avelumab

A
  • Targets PD-1
  • Merkel cell carcinoma, urothelial carcinoma
27
Q

Durvalumab

A
  • Targets PD-1
  • Urothelial carcinoma
28
Q

Relatilimab

A
  • Targets LAG-3
  • Unresectable or metastatic melanoma given in combination with nivolumab
29
Q

What are some limitations of checkpoint blockade?

A
  • More basic science needed-identify the best rationale for blockade combinations
  • T cell infiltration-getting antigen-specific T cells into tumors
  • Will NOT be particularly beneficial for cancers with low mutational burden
30
Q

Lymphodepleting chemotherapy

A
  • Fludarabine at 30 mg/m2 IV daily for 4 days
  • Cyclophosphamide at 500 mg/m2 IV daily for 2 days starting with the first dose of fludarabine
  • Kymriah is infused 2 to 14 days after completion of lymphodepleting chemotherapy
31
Q

What is the mechanism of lymphodepleting chemotherapy?

A

Mechanism is unknown
* Inudction of cytokines that promote CD3+ lymphocyte homeostasis
* Tumor burden reduction

32
Q

What CAR T cells eliminate cancers of B cell lineage?

A

CD19-directed

33
Q

What is the target and costimulatory domain of Tisagenlecleucel (Kymirah)?

A
  • Target: CD19
  • Co-stimulatory: 4-1BB
34
Q

What is the target and costimulatory domain of Axicabtagene ciloleucel (Yescarta)?

A
  • Target: CD19
  • Co-stimulatory domain: CD28
35
Q

What is the target and costimulatory domain of Brexucabtagene autoleucel (Tecartus)?

A
  • Target: CD19
  • Co-stimulatory domain: CD28
36
Q

What is the target and costimulatory domain of Lisocabtagene maraleucel (Breyanzi)?

A
  • Target: CD19
  • Co-stimulatory domain: 4-1BB
37
Q

What is the target and costimulatory domain of Idecabtagene vicleucel (Abecma)?

A
  • Target: BCMA
  • Co-stimulatory domain: 4-1BB
38
Q

What is the target and costimulatory domain of Ciltacabtagene (Carvykti)?

A
  • Target: BCMA x2
  • Co-stimulatory domain: 4-1BB
39
Q

Cytokine release syndrome (CRS)

A
  • A common complication of CD-19-directed CAR T cellls
  • Common first 2 weeks after infusion
40
Q

Prodromal Syndrome

A
  • Low-grade fever, fatigue, anorexia
  • Treatment: Observe in person
41
Q

Overt CRS

A

One or more of the following:
* High fever
* Hypoxia
* Mild hypotension
Treatment: Administer antipyretics, oxygen, intravenous fluids and/or low-dose vasopressors

42
Q

Severe of Life-threatening CRS

A

One or more of the following:
* Hemodynamic instability despite intravenous fluids and vasopressor support
* Worsening respiratory distress
* Rapid clinical deterioration
Treatment: Administer high dose or vasopressors, oxygen, mechanical ventilation
* Administer tocilizumab

43
Q

What is a common complications of CD19-directed CAR T cells?

A

Neurotoxicity
(not responsive to tocilizumab)

44
Q

How do you treat a grade 2 and 3 neurotoxicity?

A

Dexamethasone 10 mg IV q6h
* continue until grade 1 than taper over 3 days

45
Q

How do you treat grade 4 neurotoxicity?

A

Methylprednisolone 1000 mg IV for 3 days, then manage as above

Oncology (14 decks)

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