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PDAT4 > 18 - Cancer Immunotherapies > Flashcards

18 - Cancer Immunotherapies Flashcards

1
Q

Naming Monoclonal Antibodies

A

Prefix
Unique Sounding Name

Substem A
Indicates TARGET/Disease Class

Substem B
Indicates the SOURCE of AB
xi = Chimeric // xizu = chim-human // ZU = HUMANIZED

  • *Suffix**
  • mab for monoclonal antibodies
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2
Q

Rituximab
Tumor Directed Monoclonal Antibodies

A

1st FDA approved MAB to treat cancer
B-cell Non-Hodkin’s Lymphoma

Targets CD-20 = B-cell surface AG

Clinical Considerations:
Infusion related RXN = Chimeric (-xi)
Hepatitis B Reactivation
Tumor Lysis Syndrome (allopurinol for prophylaxis)

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3
Q

RituximabHYCELA

A

SUBCUTANEOUS INJECTION
version of Rtuximab

LESS INCIDENCE OF INFUSION RELATED REACTIONS

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4
Q

Moderate Infusion Reaction
Tumor Directed Monoclonal Antibodies

A

STOP infusion –> measure vitals

Administer:
Corticosteroids
+/-
H1/H2 blockers if sysmptoms persist

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5
Q

SEVERE Infusion Reaction = Anaphylaxis
Tumor Directed Monoclonal Antibodies

A

Stop Infusion -> measure vitals

Aminister:
Hydration + Corticosteroids +/- H1-2 Blockers

EPINEPHRINE + BRONCHODIALATORS

RECHALLENGE
in context of desensitization

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6
Q

Antibody-Drug Conjugates
Tumor Directed Monoclonal Antibodies

A

Antibody LINKED w/ CYTOTOXIC AGENT

AB –> targeted towards tumor tissue

Linker –> labile connection between both

Cytotoxic Agent –> kills target cells
normally toxic agent, but directed towards tumor tissue

DELIVERS CYTOTOXIC AGENT INSIDE THE CELL

Ex.
Kadcycla

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7
Q

Anti CTLA-4 Antibody
ImmunoTherapy - Monoclonal Antibodies

A

Ipilimumab

AB that Targets CTLA-4 –> STOPS inhibition of T-cell Killing
Allows for CD28–>B7 = Costim signal

FATAL IMMUNE RELATED ADVERSE REACTIONS
6 Main groups:
LEGS + Hep/Neurologic

Pharmacists are CRITICAL in educationg patients of the Signs & symptoms of ADRs

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8
Q
  • *FATAL IMMUNE-related ADR’s** of
  • *Ipilimumab** = Monoclonal AB to CTLA-4

Dermatologic

A

LEGS + HEP/Neurologic

Skin = Most common
Pruitis / Rash
Manage w/ Oral Antipuritics

  • *Grade 3/4
  • -> TOPICAL +/- ORAL CORTICOSTEROIDS**
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9
Q
  • *FATAL IMMUNE-related ADR’s of**
  • *Ipilimumab** = Monoclonal AB to CTLA-4

GASTROINTESTINAL

LEGS (reverse) + Hep/Neuro

A

Rule out other causes first

S/Sx:
Diarrhea / Ab Pain / Blood+mucus in Stool / Ileus

Management:
CORTICOSTEROIDS for prolonged Grade 2 (>1week)
or any grade 3/4

DISCONTINUE for GRADE 3/4

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10
Q
  • *FATAL IMMUNE-related ADR’s of**
  • *Ipilimumab** = Monoclonal AB to CTLA-4

ENDOCRINE

LEGS (reverse) + Hep/Neuro

A

Monitor: TSH Q6 weeks // T4 prn

Affects:
Pituitary / Adrenal Glands / Thyroid

S/Sx:
Fatigue / Headache / Abnormal Thyroid Test / Hypotension

Management:

  • *WITHOLD TREATMENT**
  • *Treat Thyroid issue**
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11
Q

FATAL IMMUNE-related ADR’s of
Ipilimumab = Monoclonal AB to CTLA-4

PULMONARY (Lungs)

LEGS (reverse) + Hep/Neuro

A

Monitor:
S/Sx of Dyspnea / Cough or SOB

Pneumonitis
onset is 2-3 mo after initiation

Management:

  • *WITHOLD TREATMENT**
  • *CORTICOSTEROIDS**
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12
Q
  • *FATAL IMMUNE-related ADR’s of**
  • *Ipilimumab =** Monoclonal AB to CTLA-4

Hepatic / Neurologic

LEGS (reverse) + Hep/Neuro

A

Hepatic:
LFT prior to each dose

Neurologic:
S/Sx of NUMBNESS / Tingling / Weakness

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13
Q

What does:
RECIST / iRECIST
measure?

A

MEASURES THE RESPONSE
to the immunotherapy

uiCR: disappearance of all lesions

uiPR: ≥ 30% decrease from baseline

uiSD: When neither PR nor PD can be established

uiPD: ≥ 20% increase from the nadir of total tumor burden

uiUPD: Unconfirmed progressive disease

uiCPD: Confirmed progressive disease

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14
Q

PSEUDOPROGRESSION

A

ACUTE RISE –> then DROP

After Immunotherapy

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15
Q

PD-1 / PD-L1 ANTAGONIST
Monoclonal ANtibodies

A

Cancer Cell’s PD-L1 –> T-cell’s PD-1
results in Negative Regulation of T-cell –> Stop Killing = Anergy

Monoclonal Antibodies INHIBIT the interaction
to continue T-cell activation / tumor cell death

Dosing Q3-4 Weeks

  • *AVOID STEROIDS**
  • reduce the T-cell count, need to inhibit the T-cells*

ADR are less severe than Ipilimumab

Monitoring / Toxicity Management is SIMILAR

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16
Q

Co-Administration of
AB’s for PD-1 /PD-L1 & CTLA-4

A

GREAT RESULTS

  • BUT*
  • *Greater TOXICITY / ADR**
17
Q
  • *BiTEs**
  • *Bi-Specific T-cell Engagers**
A

BLINATUMOMAB

Combination via Linker of:
CD-19 Single Chain AB + CD-3 AB

Connects T-CELLS to B-CELLS

Indicated for ALL
Continuous Infusion for 28 days –> 14 days off

ADR:
CYTOKINE RELEASE SYNDROME
Neurotoxicity

18
Q

CYTOKINE RELEASE SYNDROME
ADR of
BiTEs = Blinatumomab

A

Occurs when:
LARGE # of lymphocytes activate –> CYTOKINE RELEASE
IFN-Y / TNF-A

IL’s 2 - 6 - 8 - 10

Symptom onset = Days - Weeks

Symptoms:
HA / Fever / Rash
NV / HypoTension / Fatigue
Dyspnea / Tachycardia

19
Q

TREATMENT for CYTOKINE RELEASE SYNDROME
ADR of BiTEs = Blinatumomab

A

Grade 1 or 2
Supportive Care

Grade 3 or 4
Supportive Care
TOCILIZUMAB
+/- Corticosteroids

20
Q
  • *TOCILIZUMAB**
  • *ACTEMRA**
A

Treatment for Grade 3/4 CYTOKINE RELEASE SYNDROME
from BiTEs = Blinatumomab

IL-6 Receptor Antagonist
reduces cytokine & acute phase reactant production

IM -> RA
IV -> CART-cell induced cytokine release syndrome

Reverse Dosing = Max -800mg
<30 kg = 12 mg/kg
>30 kg = 8mg/kg

21
Q

NEUROTOXICITY
ADR of
BiTEs = Blinatumomab​

A

Occurs in 2 OUT OF 3 patients

Symptoms occur within 1st 8 weeks
tied to cytokine release syndrome

Symptoms are Transient, will resolve
Dont drive for 8 weeks

Symptoms:
HA / Encephalopathy / Cognate Fxn
Convulsion / Tremor / Anxiety
Loss of Coordination + Balance

22
Q

CAR-T Therapy
ADR’s

A

Cytokine Release Syndrome
79% incidence, avg 3 days to present

Neurotoxicity

Anaphylaxis
due to mouse-derived proteins

“On-Target - OffTumor” Toxicity
failure of b-cell development

23
Q

Kymriah DOSING
Tisagenlecleucel

A
  • *CAR-T Therapy**
  • *DOSE BASED ON CELL COUNT**
  • *Premedicate with APAP + DIPHENHYDRAMINE**
  • *30-60 min prior to infusion**

ALL < 25 years
≤50 kg: 0.2-5 x 106 CAR-positive viable T cells per kg
>50 kg: 0.1-2.5 x 108 CAR-positive viable T cells per kg

  • *DLBC =** diffuse large b-cell cancer
    0. 6to 6 x 108 CAR-positive viable T cells (along with chemotherapy)
24
Q

YESCARTA DOSING
Axicabtagene

A

CAR-T Therapy

Premedicate w/ APAP 650mg & DIPHENHYDRAMINE 12.5mg
60 min prior​

Large B-cell lymphoma
Target does 2 x 106 CAR-positive viable T cells per kg (max: 2 x 108)

DOSE based on CELL COUNT

PDAT4 (34 decks)

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