AOCNP Immunotherapy and Targeted Therapy 5 — Questions and Answers
Question 1: A patient on ipilimumab develops grade 2 immune-mediated colitis with 4–6 loose stools per day. Which intervention is most appropriate?
- Continue ipilimumab with antidiarrheal agents only
- Hold ipilimumab and initiate oral prednisone 0.5–1 mg/kg/day (Correct answer)
- Permanently discontinue ipilimumab and observe
- Add a second checkpoint inhibitor to boost antitumor response
Correct answer: Hold ipilimumab and initiate oral prednisone 0.5–1 mg/kg/day
Grade 2 immune-mediated colitis requires holding the offending agent and starting oral corticosteroids at 0.5–1 mg/kg/day.
Question 2: Which targeted therapy requires RET fusion testing prior to use in NSCLC?
- Osimertinib
- Selpercatinib (Correct answer)
- Crizotinib
- Dabrafenib
Correct answer: Selpercatinib
Selpercatinib is a selective RET inhibitor indicated for NSCLC with RET fusions, which must be confirmed by molecular testing.
Question 3: A patient receiving atezolizumab develops new-onset polyuria, polydipsia, and hyperglycemia. Which immune-related endocrinopathy should be suspected?
- Hypothyroidism
- Adrenal insufficiency
- Type 1 diabetes mellitus (Correct answer)
- Hypophysitis
Correct answer: Type 1 diabetes mellitus
Checkpoint inhibitors can trigger autoimmune type 1 diabetes, presenting with new hyperglycemia and symptoms of insulin deficiency.
Question 4: Trastuzumab emtansine (T-DM1) is classified as which type of targeted agent?
- Checkpoint inhibitor
- PARP inhibitor
- Antibody-drug conjugate (Correct answer)
- CDK4/6 inhibitor
Correct answer: Antibody-drug conjugate
T-DM1 is an antibody-drug conjugate that links trastuzumab to the cytotoxic agent DM1, delivering chemotherapy selectively to HER2-overexpressing cells.
Question 5: Which statement best describes the role of tumor mutational burden (TMB) in immunotherapy?
- High TMB predicts resistance to PD-1/PD-L1 inhibitors in all cancers
- High TMB is associated with more neoantigens and potentially greater response to checkpoint inhibitors (Correct answer)
- TMB is used to select patients for EGFR-targeted therapy
- Low TMB is required for CAR-T cell eligibility
Correct answer: High TMB is associated with more neoantigens and potentially greater response to checkpoint inhibitors
Tumors with high TMB produce more neoantigens, which can be recognized by the immune system, potentially enhancing response to checkpoint inhibitors.
Question 6: A patient on crizotinib for ALK-rearranged NSCLC develops disease progression after 12 months. Which next-generation ALK inhibitor is most appropriate?
- Erlotinib
- Alectinib (Correct answer)
- Vemurafenib
- Rucaparib
Correct answer: Alectinib
Alectinib is a next-generation ALK inhibitor with activity against many crizotinib-resistance mutations and better CNS penetration.
Question 7: Which adverse effect is most uniquely associated with immune checkpoint inhibitor–induced myocarditis compared to other irAEs?
- It is one of the most common irAEs, occurring in >20% of patients
- It carries one of the highest fatality rates despite low incidence (Correct answer)
- It responds poorly to corticosteroids and requires permanent management
- It only occurs with anti-CTLA-4 agents, not PD-1 inhibitors
Correct answer: It carries one of the highest fatality rates despite low incidence
Immune-mediated myocarditis is rare but has a fatality rate up to 25–50%, making early recognition and aggressive treatment critical.
AOCNP Immunotherapy and Targeted Therapy 5
A patient on ipilimumab develops grade 2 immune-mediated colitis with 4–6 loose stools per day.
Which intervention is most appropriate?