Biologic Response Modifiers Flashcards


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1

5 classes of immunoglobulin

IgG, IgM, IgA, IgD, IgE

2

What is antibody-dependent cell-mediated cytotoxicity (ADCC)

A type of immune reaction in which a target cell or microbes is coated with antibodies and killed by certain types of white blood cells. The white blood cells bind to the antibodies and release substances that kill the targets cells or microbes

3

Characteristics of major histocompatibility complex

set of surface proteins located on the cell membrane of nucleated cells, identifies the antigen between self and non-self, responsible for antigen presentation

4

What MHC class is Th (CD4+)

MHC class II

5

What MHC class is Tc (CD8+)

MHC class I

6

How do monoclonal antibodies work

binds to either the extracellular receptor or its natural ligand and prevent the activation of downstream intracellular signaling

7

Types of monoclonal antibodies

murine, chimeric, humanized, or human

8

mAb is designed to target a pathway critical for the

survival and growth of cancer cells

9

Cytotoxic T-cell lymphocyte antigen-4 (CTLA-4) inhibitors MOA

CTLA-4 and CD28 bind to B7; however, CTLA-4 has a higher affinity for the ligand and outcompetes the B7/CD28 stimulating interaction (the second signal of T-cell activation). The CTLA-4/B7 interaction inhibits T-cell proliferation and downregulates expression of IL-2 production in immune cells, inhibiting the third signal of T-cell activation. Blocking CTLA-4 with ipilimumab and, thus, releasing B7 for interaction with CD28 causes activation of T-cells against tumor cells

10

PD-1 (programmed death protein-1) and PD-L1 (programmed death ligand-1) inhibitors MOA

When PD-1 binds to its ligands PD-L1 or PD-L2, it serves as a coinhibitory signal to inhibit immune function. The binding inhibits T-cell proliferation and downregulates expression of the antiapoptotic molecule Bcl-xL, cytokine expression, and the mTOR pathway in immune cells. Because PD-1 is also expressed on B-cells, it could amplify antibody production. Binding of nivolumab or pembrolizumab to PD-1 inhibits binding of the receptor to its ligands PD-L1 and PD-L2 on tumor cells,
inhibits the coinhibitory signal on T-cells, reverses T-cell suppression, and induces antitumor response.

11

CTLA-4 inhibitors drugs

Ipilimumab, Tremelimumab

12

PD-1 inhibitors drugs

Pembrolizumab, Nivolumab, Cemipilimab, Dostarlimab

13

PD-L1 inhibitors drugs

Atezolizumab, Avelumab, Durvalumab

14

CTLA-4 inhibitors are frequently used in combination with

PD-1 or PD-L1 inhibitors

15

What is the purpose of immunotherapy biomarkers

to identify patients that may benefit from immunotherapy

*predicts response to immune checkpoint inhibitors*

16

What are some immunotherapy biomarkers

tumor mutational burden (TMB), microsatellite instability (MSI), programmed death ligand (PD-L1)

17

What is TMB

The approximate amount of gene mutation that occurs in the genome of a cancer cell. Elevated TMB is correlated with higher neoantigen expression which helps the immune system recognize tumors

18

Define neoantigen

A new protein that forms on cancer cells when certain mutations occur in tumor DNA

19

What is MSI

Deficient mismatch repair (dMMR) and its characteristic genetic signature, high levels of microsatellite instability correlates with higher neoantigen expression which helps the immune system recognize tumors (patients with MSI are more likely to respond to immunotherapy)

20

How to calculate tumor proportion score (TPS)

# of PD-L1 positive tumor cells/ total # of viable tumor cells X 100

21

How to calculate combined positive score (CPS)

# of PD-L1 positive cells (tumor cells, lymphocytes, macrophages)/ total # of viable tumor cells X 100

22

What is TPS

a PD-L1 measurement which is applied to lung cancer, head and neck cancer and melanomas.

23

What is CPS

evaluated based on the number of PD-L1 positive cells (tumor, lymphocytes and macrophages) in relation to total tumor cells

24

Define pseudoprogression

an initial increase in tumor size is observed or new lesions appear, followed by a decrease in tumor burden

25

Most common adverse events for immune checkpoint inhibitors

fatigue, rash, diarrhea, myalgias/arthralgias

26

Rare but serious adverse events for immune checkpoint inhibitors

colitis, pneumonitis, endocrinopathies, hepatitis, nephritis

27

Grade 1 general management of IRAEs (immune-related adverse events)

  • continue immunotherapy with close monitoring (exceptions:neurologic, hematologic, cardiac toxicities)

28

Grade 2 general management of IRAEs (immune-related adverse events)

  • hold immunotherapy for most toxicities, resume when resolved to ≤ grade 1
  • prednisone PO 0.5-1 mg/kg/day or equivalent may be administered

29

Grade 3 general management of IRAEs (immune-related adverse events)

  • hold immunotherapy
  • start prednisone PO 1-2 mg/kg/day or methylprednisolone IV 1-2 mg/kg/day with taper over ≥ 4-6 weeks
  • if no improvement after 48-72 hours, consider more aggressive immunomodulatory agents (infliximab)

30

Grade 4 general management of IRAEs (immune-related adverse events)

  • generally permanently discontinue immunotherapy (Except for endocrine therapy controlled by hormone replacement)

31

Define bullous dermatitis

large fluid filled blisters

32

Define maculopapular rash

red, flat area on the skin covered with small confluent bumps

33

Grade 1 maculopapular rash management

continue immunotherapy-> topical emollient-> oral antihistamine-> treatment with moderate potency topical steroids to affected areas

34

Grade 2 maculopapular rash management (papules, macules covering 10% to 30% BSA with or without symptoms)

continue immunotherapy-> topical emollient-> oral antihistamine for pruritus-> treatment with moderate to high potency topical steroids to affected areas-> if unresponsive to topical, consider prednisone 0.5 mg/kg/day

35

Grade 3-4 maculopapular rash management

hold immunotherapy-> treatment with moderate to high potency topical steroids to affected areas-> prednisone 0.5-1 mg/kg/day (increase to 2 mg if no improvement)-> urgent dermatology consultation, consider biopsy-> consider inpatient care

36

What is TSH

stimulates thyroid gland to make more thyroid hormone

37

What is free T4 (thyroxine)

converted into T3- active form makes T4 in response to TSH

38

Symptoms of hypothyroidism

fatigue, lethargy, sensation of being cold, constipation

39

What is the hypothyroidism management for TSH between 4 to <10, patient is asymptomatic and normal free T4

continue immunotherapy and continue to monitor thyroid function test (TFTs)

40

What is the hypothyroidism management for TSH >10 and normal free T4

continue immunotherapy and consider levothyroxine

41

Grade >1 colitis management

hold immunotherapy-> initiate treatment with methylprednisolone IV if possible-> if no response in 2-3 days consider adding infliximab or vedolizumab within 2 weeks

42

Grade ≥ 3

admit inpatient-> discontinue anti CTLA-4 permanently, if G4 discontinue anti PD-1/PD-L1 permanently

43

GI prophylaxis supportive care

≥ G2: PPI or H2RA

44

Infection supportive care

>20 mg/day prednisone

  • >4 weeks: PJP (bactrim)
  • >6 weeks: fungal (fluconazole)
  • consider prophylaxis against HSV (acyclovir)

45

Osteopenia supportive care

steroids >12 weeks: calcium and vitamin D supplementation