Immune Checkpoint Inhibitors

List the PD1 inhibtors and their MOA

Pembrolizumab, Nivolumab, Cemiplimab-rwlc, Dostarlimab-gxly

• Normally, cancer cells use a protein called PD-L1 to bind to PD-1 and hide from the immune system.

• These are Highly selective antibodies that bind to (block) PD1 receptor on found on T cells keeping T cells active so they can recognize and attack the cancer.

List the PD-L1 inhibitors and their MOA

Atezolizumab, Durvalumab, Avelumab

• Block the PD-L1 protein on cancer cells.

• This prevents cancer cells from sending the “off” signal to T cells, allowing the immune system to stay active and destroy the cancer.

List the CTLA-4 inhibitors and their MOA

Ipilimumab and tremelimumab

• CTLA-4 protein on T cells normally acts like a brake to slow them down.

• By blocking CTLA-4, these drugs allow for enhanced T cell activation and proliferation

What is the black box warning for Ipilimumab?

immune mediated adverse reactions

• These side effects happen because Ipilimumab ramps up the immune system, which can sometimes lead it to attack healthy organs

monitoring

HbA1C
Derm screening
Pancreatitis
Thyroid
Hormones (LH, FSH, Testosterone, Estradiol, ACTH)
EKG

Drug interactions with immune checkpoint inhibitors

antibiotics, steroids, PPIs

vemurafenib (hepatotoxicity)- CTLA4 inhibors only

What toxicites are associated with immune checkpoint inhibitors? Which toxicites show up earlier? What makes them more severe?

Sooner: Rash. Colitis, Endocrinopathy
Later: Liver toxicity, pneumonitis, nephritis

These meds have a long half life so side effects can happen a year or more beyond

Combo & CTLA4 AEs are worse

What is the GRADE for dermatologic IRAE

Grade	Symptoms	Body Coverage (BSA)
1	Itchy or tender rash, easily controlled with creams or pills	Less than 10%
2	Rash affects daily activities, needs treatment	10–30%
3	Rash doesn't improve with treatment, may need antibiotics	More than 30%
4	Rash is unmanageable, may be life-threatening and need IV antibiotics	Any amount

Rash BSA calculation

Head, Arms: 9%
Front torso, back torso, right leg, left leg: 18%

Arms and legs: Split front or back by 50%

ex: only front of right leg is 9%

Dermatologic IRAE Management

Grade 3-4: Admit for IV corticosteroid

Methylprednisolone to prednisone conversion

Methylpred is 0.8mg = 1 mg prednisone

What are the normal limits for AST, ALT

AST: 13-44
ALT: 8-66

Hepatisits 4 grades and management

What drug should not be used in hepatits

infliximab

Why are two checkpoint inhibitors often used instead of just one?

because they target different parts of the immune response, leading to a stronger and broader activation of the immune system against cancer.