Intro to Immunotherapy

Question 1

Checkpoint Inhibs MOA :

1. How are cancer cells able to evade T cells?
2. How do drugs such as checkpoint inhibitors/immunotherapy prevent T cell deactivation ?

Answer 1

1. They have proteins that allow them to resemble healthy cells , one protein is PDL1. When T cells use PD1 proteins to latch onto cancer PDL1, their function gets inhibited, leading to immunosuppression
2. Immunotherapy drugs block the PD1/PDL1 interaction so that tumor cells can no longer deactivate the t cells

Question 2

What’s the target of agents such as Nivolumab, Pembrolizumab and Avelumab?

targets of Atezolizumab and Durvalumab ?

Answer 2

PD-1

PD-L1

Question 3

What are the adverse effects of Immunotherapy? (4)

When do these ae’s start to occur and last for?

How is this diff from cytotoxic chemo?

Answer 3

1. Rash, itching
2. Hepatitis
3. Colitis
4. Inflamm of the endocrine organs

Ae’s of immunotherapy : They start after a couple of WEEKS and last for weeks

Cytotoxic chemo ae’s will begin in days

Question 4

Immunotherapy Related Side Effects

1. GI
2. Liver
3. Skin
4. Lungs
5. Brain/nerves
6. Hormones

Answer 4

1. Diarrhea, belly pain, blood/mucus in stool, inability to pass stool
2. Incr in liver function tests, yellowing of skin and or eyes
3. Rash/itching
4. worsening SOB and or cough , fever
5. Weakness, tingling/pins and needles in hands and feet , difficulty walking/picking up things
6. Low energy levels, changes in mental function, HA, belly pain, decr in BP, changes in thryoid function tests

Question 5

Monitoring Immunotherapy - Baseline and prior to each dose (KNOW THIS)
1. CBC such as ? (5)
2. CMP such as ? (3)
3. Thyroid function such as ? (2)
4. C
5. O
6. E
7. PFTS in some pt’s such as?
8. PE including ? (4)

Answer 5

1. WBC, Hgb, Hct, PLT, ANC
2. Electrolytes (K, Na, Mg) , LFTS
   -Blood sugars
3. TSH, FT4
4. Cortisol
5. O2 saturation
6. ECG in select pt’s
7. ILD, COPD, prior tx related lung toxicity
8. Bowel habits, neuro exam, Joiint exam/functional asessment, oral care

Question 6

Immunotherapy Common AE’s : For each grade, state what u would do

1. Maculopapular Rash Grade 1-3
2. Pruritis Grade 1-3

Answer 6

1. Grade 1 : Continue immunotx, topical moisturizers, oral ANTIHISTAMINE , Triamcinolone 0.1% cream to AA BID

Grade 2: COntinue immunotx, topical moisturizers, oral ANTIHISTAMINE , Triamcinolone 0.1%/Clobetasol 0.05% cream to AA BID

Grade 3/4 : DC immunotx. Clobestasol 0.05% AA BID, Pred 0.5-1mg/kg/day , Derm consult

2. Grade 1 : Continue immunotx, oral ANTIHISTAMINE , Triamcinolone 0.1% cream to AA BID ,
   !!! Lidocaine patches!!

Grade 2 : Continue immunotx, oral ANTIHISTAMINE , Triamcinolone 0.1%/Clobetasol 0.05% cream to AA BID ,
!!!consider Gabapentin/pregabalin!!

Grade 3-4 : DC immunotx, Oral antihist, Pred 0.5-1mg/kg/day,
Aprepitant or omalizumab for refractory cases!, urgent derm consult

Question 7

IRAE’s Hypothyroidism Diagnosis / Workup and management

1. Clinical primary hypothyroidism
2. Asx/Sub clinical hypothyroidism :

a. For what lab values would u consider continuing immunotx, and monitoring TFT labs q4-6weeks

b.For what lab values would u consider continueing immunotx, CONSIDERING levothyroxine 1.6mcg/kg/day and cont monitoring TFT labs?

c. For what lab values would you USE levo 1.6 mcg/kg/day and continue monitoring TFT labs?

Answer 7

1. Diagnosis : Continue immunotx, consider endo consult, levothyroxine 1.6 mcg/kg/day, continue to monitor TFT labs q4-6weeks

2A. TSH 4-10, Asx , Normal FT4

2B. TSH > 10 , Normal FT4

2C. Normal or low TSH, low FT4

Question 8

1. Whats the MOST COMMON ADE of immunotherapy?
2. How would u work this state up?
3. grade 1 (Mild relieved by rest)
4. Grade 2 (moderate = NOT relieved by rest, limiting ADLs)
5. Grade 3-4 (Severe, not reliieved by rest, limiting self care)

Answer 8

1. Fatigue
2. PE, CBC for Hgb, CMP, TSH, FT4, Morning cortisol, Morning ACTH if AM cortisol abnormal, AM testosterone in males, med review
3. Continue immunotx, consider consultations based on workup
4. continue immunotx if impact on ADL can be mitigated by active management
   -COnsider consults based on workup
   -If NO treatable cause, consider low dose steroid trial
   -Consider close follow up in 5-7 days
   -Address lab or vital abnormalities
   -COnsider disease progression or other med condition
5. DC IMMUNOTX!
   -COnsider consultations based on workup
   -Consider disease progression, other med condition , or other IRAE

Question 9

CAR T Cells :
1. What does CAR stand for?
2. How are the t cells able to identify and target tumor cells?

Answer 9

1. Chimeric antigen receptor
2. They’re re-programmed T cells that are genetically re-engineered in a lab and these t cells are infused back to pt.

Question 10

AE’s of CAR-T cells

1. If tumor associated antigen to which CAR is targeted is expressed on normal tissues, what happens?
2. two other ae’s

Answer 10

1. Normal tissues may be damaged by CAR T cells
2. Cytokine release syndrome (CRS) –> lots of stuff can happen in every organ

• Neurologic Toxicity
  HA, COnfusion, alt in wakefulness, hallucinations, dysphasia, ataxia , tremor, seizures

Question 11

What do we use to treat CRS ?
WHat is it fda approved for?

Answer 11

Tocilizumab (IL6 receptor antag)

To tx rheumatologic disorders –> used off label for toxicity following CAR-T cells infusions