AOCNP Immunotherapy and Targeted Therapy 1 — Questions and Answers
Question 1: Which class of immunotherapy works by blocking the PD-1/PD-L1 checkpoint pathway to restore anti-tumor T-cell activity?
- CAR-T cell therapy
- Checkpoint inhibitors (Correct answer)
- Monoclonal antibodies targeting HER2
- Cytotoxic T-lymphocyte vaccines
Correct answer: Checkpoint inhibitors
Checkpoint inhibitors such as pembrolizumab (anti-PD-1), nivolumab (anti-PD-1), and atezolizumab (anti-PD-L1) block inhibitory signals that tumor cells use to suppress T-cell activity, thereby restoring the immune system's ability to recognize and destroy cancer cells.
Question 2: Imatinib (Gleevec) is a tyrosine kinase inhibitor (TKI) that targets which molecular abnormality in chronic myelogenous leukemia (CML)?
- EGFR mutation
- BCR-ABL fusion protein (Correct answer)
- HER2 amplification
- ALK rearrangement
Correct answer: BCR-ABL fusion protein
Imatinib specifically inhibits the BCR-ABL tyrosine kinase produced by the Philadelphia chromosome (t(9;22) translocation) in CML. It was the first targeted therapy to demonstrate that molecular targeting of a cancer driver mutation could produce durable remissions.
Question 3: A patient receiving pembrolizumab develops severe, grade 3 immune-related pneumonitis. What is the most appropriate initial management?
- Continue pembrolizumab at reduced dose
- Permanently discontinue pembrolizumab and start high-dose corticosteroids (Correct answer)
- Hold pembrolizumab and begin inhaled corticosteroids
- Switch to a different checkpoint inhibitor
Correct answer: Permanently discontinue pembrolizumab and start high-dose corticosteroids
Grade 3–4 immune-related pneumonitis requires permanent discontinuation of the checkpoint inhibitor and initiation of high-dose systemic corticosteroids (prednisone 1–2 mg/kg/day or methylprednisolone IV), with pulmonology consultation. This is a potentially life-threatening irAE.
Question 4: Which biomarker must be tested before initiating trastuzumab (Herceptin) therapy for breast cancer?
- KRAS mutation status
- HER2 overexpression or gene amplification (Correct answer)
- EGFR mutation
- PD-L1 expression level
Correct answer: HER2 overexpression or gene amplification
Trastuzumab targets the HER2 (human epidermal growth factor receptor 2) protein. HER2 testing by IHC (3+ overexpression) and/or FISH/ISH (gene amplification) is mandatory before initiating trastuzumab, as it is only effective in HER2-positive tumors (~15–20% of breast cancers).
Question 5: Cytokine release syndrome (CRS) is a potentially life-threatening toxicity most commonly associated with which type of immunotherapy?
- PD-1 checkpoint inhibitors
- CAR-T cell therapy and bispecific T-cell engagers (Correct answer)
- Anti-VEGF monoclonal antibodies
- PARP inhibitors
Correct answer: CAR-T cell therapy and bispecific T-cell engagers
CRS occurs when large numbers of immune cells are activated and release excessive cytokines (especially IL-6, IFN-γ), causing fever, hypotension, and hypoxia. It is most severe with CAR-T therapies (e.g., tisagenlecleucel) and bispecific T-cell engagers (e.g., blinatumomab). Tocilizumab is the treatment of choice for severe CRS.
Question 6: EGFR-mutated non-small cell lung cancer (NSCLC) is most effectively treated with which class of targeted agents?
- VEGF inhibitors (bevacizumab)
- EGFR tyrosine kinase inhibitors (e.g., osimertinib) (Correct answer)
- ALK inhibitors (e.g., crizotinib)
- KRAS G12C inhibitors (e.g., sotorasib)
Correct answer: EGFR tyrosine kinase inhibitors (e.g., osimertinib)
EGFR TKIs, particularly third-generation osimertinib, are first-line standard of care for EGFR-mutated (exon 19 deletion or L858R) NSCLC. Osimertinib also covers T790M resistance mutations and has better CNS penetration compared to first/second-generation TKIs.
AOCNP Immunotherapy and Targeted Therapy 1
Which class of immunotherapy works by blocking the PD-1/PD-L1 checkpoint pathway to restore anti-tumor T-cell activity?