Immuno-Oncology Flashcards
What are the 5 pillars of cancer care?
- Radiotherapy
- Surgery
- Traditional chemotherapy
- Precision therapy
- Immunotherapy
What is immuno-oncology (IO)? (2)
- Development and delivery of therapies that improve immune response against cancer
- Provides immune system with tools to recognize tumours and strengthen tumour attack
What is the goal of IO therapy?
Restore or enhance anti-tumor immune responses
Generally, what is the MOA of IO agents? (2)
- Mark cancer cells for immune system recognition and destruction
- Enhance immune system response against the cancer
Side effects of IO therapy are ______-_______ and can affect any organ
immune-related
What are the different types of IO therapy? (6)
- MABs
- Adoptive T-cell transfer
- Cytokines
- Treatment vaccines
- Bacillus Calmette-Guerin (BCG)
- Toll-like receptor agonists
Should know how IO therapy differs from chemotherapy and targeted molecular therapy
- Chemotherapy:
- Acts directly on cancer cells that are actively reproducing (ie, in the cell cycle)
- Often causes tumour cell death vs simply inhibiting tumour growth - Targeted Therapy:
- Inactivates specific proteins in tumour cells that are involved in the growth, progression and spread of cancer - IO Therapy (Checkpoint inhibitors):
- Triggers the immune system to destroy cancer cells
- Considered a type of targeted therapy
What is the 1 CTLA4 inhibitor drug to know?
Ipilimumab
What are the 2 PD-1 inhibitor drugs to know?
- Pembrolizumab
- Nivolumab
What are the 3 PD-L1 inhibitor drugs to know?
- Durvalumab
- Atezolizumab
- Avelumab
Where is the site of activity of CTLA-4 inhibitors?
Lymph node (regulates T-cell proliferation early in immune response)
Where is the site of activity of PD-1/PD-L1 inhibitors?
Cancer cell (T-cell proliferation later in immune response and in the periphery)
Explain the MOA of CTLA4 inhibitors? (3)
- CTLA-4 is inhibitor of T-cell function. Breaks on the immune system.
- When immune system is overstimulated, CTLA-4 normally comes out. CTLA-4 inhibitor acts right here at the CTLA-4 B7 complex, breaking this connection, thus turning off the breaks.
- T cells are active and leaving the lymph node to go and find cancer cells and try to eliminate cancer.
What are 3 indications for CTLA4 inhibitors?
- Melanoma
- Kidney cancer
- Small cell lung cancer
Explain the MOA of PD1/PD-L1 inhibitors (2)
- This is out in the tissues. T cell left lymph node, out in tissues. When finds tumor cells, connection is made between the two. PD1 receptor is on T cell, PDL1 on tumor. When they connect, the T cell thinks that the tumor cell is a friend at the moment. T cell not fighting the tumor cell at the moment. Not doing its job to destroy the tumor cell
- Break this handshake via a PD1 inhibitor, or PDL1 inhibitor. Whichever we use, as long as this handshake is broken, then T cell recognizes tumor as foreign and knows it’s job is to eradicate it.
Patient is experiencing toxicity on an IO drug. What do we do with their dose?
Either hold or give at full dose later - we do NOT reduce dose
How in general are IO agents dosed?
(Admin, interval, selecting dose)
- IV administration
- Various intervals
- Flat dosing vs. mg/kg dosing
What are some examples of IO protocols? (5)
- Single agent IO
- Atezolizumab q3w - IO + IO (CTLA-4 plus PD1)
- Ipilimumab + nivolumab - IO + IO + cytotoxics
- Ipilimumab+ + Nivolumab + cisplatin + Pemetrexed - IO + cytotoxics
- Pembrolizumab + Carboplatin + gemcitabine - IO + targeted
- Pembrolizumab + axitinib
How does targeted therapy, ipilimumab overall survial compare to chemotherapy overall survival (talking about melanoma)?
- Ipilimumab 22% 3-yr survival rate
- Maybe 1-2% long-term response with chemotherapy
What did studies find in lung cancer with Nivolumab and Pembrolizumab in terms of overall survival?
The IO drugs found to be much better than chemotherapy
What are the unique ADEs of chemotherapy compared to checkpoint blockade? (4)
- Neutropenia
- Thrombocytopenia
- Anemia
- Infection
What are the unique ADEs of checkpoint blockers compared to chemotherapy? (5)
- Rash
- Colitis
- Hepatitis
- Pneuomonitis
- Endocrinopathy
While some symptoms (ADEs) may overlap between chemotherapy and checkpoint blockade, they are mediated through _________ _________
different pathways
What are 3 potential risk factors favoring emergence of immune related ADEs?
- Personal/Family history of autoimmune disease
- Tumor infiltration
- Concomitant medications and occupational exposures
What are 3 key factors for prevention of immune related ADEs?
- HCP and patient education
- Patient reporting
- Call-back program
During IO treatment, how are immune related ADEs monitored? (2)
- Lab tests before every IO administration
- Compare values to baseline
After IO treatment termination, how are immune related ADEs monitored? (2)
- Lab tests/evaluation on 3-month basis during first year and then every 6 months
- Be aware that irAEs can develop even after discontinuation of IO treatment
What are 3 potential etiologies of ADEs in a person on IO therapy?
- Disease-related
- Incidental event
- Immune-related ADE
What should we know about the kinetics of apperance of immune related ADEs with checkpoint blockade? (4)
- Characteristic pattern in the timing of the occurrences
- For both CTLA4 and PD1 therapies, skin and GI tox occurs the earliest. While liver and endocrine tend to occur later.
- Most ADEs do not occur before first 4 weeks of therapy. Takes time for immune system to kick in and turn on.
- In some cases, might not arise until pt been on for weeks to months. High levels of suspicion advised.
With grade 1 immune related ADEs, how is immunotherapy (IO) managed?
Supportive care +/- withhold drug
With grade 2 immune related ADEs, how is immunotherapy (IO) managed?
Withhold drug, consider restart if toxicity resolves to grade ≤ 1; initiate low-dose corticosteroids (prednisone 0.5 mg/kg/day or equivalent) if symptoms do not resolve within 1 week
With grade 3/4 immune related ADEs, how is immunotherapy (IO) managed?
Discontinue drug; high-dose corticosteroids (prednisone 1-2 mg/kg/day or equivalent) taper once toxicity resolves to grade ≤ 1
Most immune related ADEs resolve with: (2)
- Temporary or permanent discontinuation of IO treatment
- Temporary immunosuppression (i.e., use of corticosteroid treatment)
Time needed for immune related ADE resolution depends on nature of toxicity. Give 2 examples
- Immunosuppression can rapidly improve GI, hepatic and renal toxicities
- Skin and endocrine toxicities require more time for resolution
Upon resolution of immune related ADEs, monitor patient for? (2)
- Symptom resolution
- Relapse/recurrence
True or False? Systemic corticosteroids do not appear to impact patient outcomes
True - this is a good thing btw - means you can manage ADEs without impacting their treatment.
What are the complications from prolonged steroid treatment?
- Prolonged, high-dose steroid use has been associated with
additional risks - Confirmed risk of opportunistic infection from steroid use in irAE management
- Optimal steroid dosing regimen for irAEs not yet established
What are some management strategies for steroid-related complications? (4)
- Monitor for signs and symptoms of steroid-related AEs
- Antibiotic prophylaxis may be warranted
- Gradual steroid tapering is important
– BCCA recommends steroid tapering over at least 1 month before
resuming IO therapy - Additional considerations:
– Vitamin D and calcium (osteoporosis risk)
▪ Some guidelines recommend vitamin D or calcium supplementation; however, recent studies have found no benefit from calcium or vitamin D supplementation
– Proton pump inhibitor (gastritis)
What is CAR-T therapy? (3)
- Similar to a transplant.
- In this case, it’s the pts own cells that are being genetically engineered to specifically fight their cancer. Own T cells extracted, there is identification of THEIR specific cancer type (personalized med type shit). Within the lab they grow T-cells with enhanced levels of CARs. Eventually, once the cells are grown within labs, shipped back here, and pts will receive some pre-conditioning chemotherapy. Their CAR-T cells will be reinfused.
- Primarily for blood cancers
What are some toxicities associated with CAR-T therapy? (4)
- B-cell aplasia
- Cytokine release syndrome (CRS)
- Neurotoxicity
- Financial
What are some risk factors for cancer-associated thrombosis? (3)
- Patient related
- Cancer related
- Treatment related
What could be given for cancer-associated thrombosis prophylaxis and treatment? (4)
- Aspirin
- LMWH
- Oral anticoagulants - DOACs
- Warfarin
For cancer-associated thrombosis prophylaxis/treatment, when is LMWH preferred? (3)
- At high risk of bleeding
- With unresected intraluminal GI or GU cancer
- With significant DDIs with DOACs
For cancer-associated thrombosis prophylaxis/treatment, when are DOACs preferred? (3)
- At low risk of bleeding
- With other cancer types
- Without significant DDIs
How long should cancer-associated thrombosis prophylaxis/treatment be?
Initially 6 months
What are some ways to manage cancer related fatigue (CRF) (7)
- Manage precipitating factors
- Energy conservation
- Exercise with moderate intensity (e.g. walking)
- Limit naps (< 1 hour)
- Reduce stress (meditation, yoga, ti chi)
- Food and water intake
- Use distractions
