Immunotherapy Flashcards
AE’s of checkpoint inhibitors
- autoimmune encephalitis
- peripheral neuropathy
- nephritis/renal failure
- cardiotoxicity (anything but high risk for conduction abnormalities)
- type 1 diabetes (irreversible)
- hypophysitis
- rash
- autoimmmune hepatitis
- hypo/hyperthyroidism
- colitis (diarrhea, abdominal pain, GI bleeding). ***Virtually any organ can be subject to autoimmunity. There all diagnosis of exclusion, must rule out infection too. Lung toxicity can be deadly if not identified early enough.
- Most common – skin rash, pruritus, colon SE’s.
Rash in immune checkpoint inhibitors
highly variable, includes SJS and bullous pemphigoid.
When to hold immunotherapy
most grade 2 toxicities, grade 3 generally
Deaths from immune checkpoint inhibitors?
very rare but have been documented.
correlation of toxicity and outcome
*Toxicity does not correlate to outcome, There is some data that if you develop toxicity, you have a higher survival rate (immune system activation).
Elderly population and immunotherapy
Data suggests they do just as well, despite immune system senescence (but this is for elderly people with high PS).
Can HIV patients be treated?
Yes, but need HIV ID specialist.
Can you treat organ transplant recipient?
Yes, but about 50% have organ rejection
Can you restart immune checkpoint blockade after AE?
Depends on severity of AE, but data is mixed on efficacy (a lot of people seem to remain in CR).
Can you treat patients with autoimmune disease?
You can but chance of flair are higher.
How to manage most SE’s of checkpoint inhibitors
→ steroids for generally at least 4 weeks + hold therapy (a few you can continue)
Management of autoimmune hepatitis as SE from checkpoint inhibitors
mycophenolate, NOT infliximab (hepatotoxic)
steroid taper for managing AE’s
4-6 weeks
Patients on immune checkpoint inhibitors also need
PPI + bactrim
general physiologic effect of immune system activation
immune system activation commonly causes an inflammatory response in normal tissue.
immune-related colitis prognosis and management
can be fatal, early diagnosis and intervention is critical. IV steroids (bioavailability).
ipilimumab MOA
CTLA4 inhibitor
tocilizumab MOA
biologic, Anti-IL-6 receptor monoclonal antibody
etanercept MOA
biologic, recombinant TNF receptor linked to IgG1 Fc portion
what are tumor infiltrating lymphocytes (TILs)?
Lymphocytes within tumor, that are then amplified and transfused back into patient. Good evidence for melanoma, and being studied for other cancer types.
How do you choose among PD-L1 CPI’s?
Basically on scheduling/dosing frequency (pembro ideal because it can be given every 6 weeks)
Best metric for predicting response to PD1/PDL1 CPI’s
Still unclear. PD-L1 expression is the most widely used currently. BUT PD-L1 may not be best marker (some patients respond well without high expression). Tumor mutational burden may be better.
How is TMB measured?
NGS
Pembro mechanism of action
monoclonal ab that binds to the PD-1 receptor on T-cells –> this blocks PD-1 ligands (PD-L1 and PD-L2) from binding –> Blocking the PD-1 pathway inhibits the negative immune regulation caused by PD-1 receptor signaling (Hamid 2013) –> this reverses T-cell suppression and induces antitumor responses
What are the checkpoint inhibitors?
- CTLA-4
- PD-1 or PD-L1
Contraindications to immunotherapy
1) connective tissue disease
2) autoimmune disease
Colitis incidence higher with which CPIs
CTLA-4 inhibitors
Reversibility of CPI toxicity
Endocrine toxicity is generally irreversible, the others are reversible
Incidence of infusion reactions with CPIs
rare.
Time course with checkpoint inhibitor toxicity
Toxicities can also happen a month after you finish drug, or even longer. Time course varies depending on organ (skin earlier, pulm later, GI earlier).
IRAE means
Immune related adverse events.
efficacy of immunotherapy in patients on steroids
- in melanoma literature, it hasn’t been associated with decreased efficacy
- however, there is data showing decreased efficacy in patients taking steroids prior to starting immunotherapy
