Harnessing targeted therapies represents a paradigm shift in oncology, moving beyond traditional chemotherapy to treatments that exploit specific vulnerabilities of cancer cells. Drugs like inotuzumab ozogamicin and blinatumomab, used in acute lymphoblastic leukemia, exemplify this approach. For PharmD students, a deep dive into the mechanisms of these advanced therapies—from antibody-drug conjugates to Bi-specific T-cell Engagers—is essential for managing complex patient care.
1. A “targeted therapy” in oncology is a drug that:
- Kills all rapidly dividing cells in the body.
- Is designed to interfere with specific molecules involved in cancer cell growth and survival.
- Is only available in oral formulations.
- Has no potential for side effects.
Answer: Is designed to interfere with specific molecules involved in cancer cell growth and survival.
2. Inotuzumab ozogamicin is an example of what type of targeted therapy?
- A small molecule kinase inhibitor
- A checkpoint inhibitor
- An Antibody-Drug Conjugate (ADC)
- A Bi-specific T-cell Engager (BiTE)
Answer: An Antibody-Drug Conjugate (ADC)
3. Blinatumomab is a Bi-specific T-cell Engager (BiTE) antibody construct. What is its unique mechanism of action?
- It delivers a cytotoxic payload directly into the cancer cell after binding to CD19.
- It simultaneously binds to CD19 on cancer cells and CD3 on T-cells, bringing them together to induce T-cell mediated cytotoxicity.
- It inhibits the production of all B-cells in the bone marrow.
- It blocks a specific intracellular signaling pathway within the lymphoblast.
Answer: It simultaneously binds to CD19 on cancer cells and CD3 on T-cells, bringing them together to induce T-cell mediated cytotoxicity.
4. The antibody component of inotuzumab ozogamicin targets which antigen on the surface of B-cell lymphoblasts?
- CD19
- CD20
- CD22
- CD3
Answer: CD22
5. The cytotoxic payload attached to inotuzumab ozogamicin is a calicheamicin derivative, which causes cell death by:
- Inhibiting a cell surface receptor.
- Causing double-strand DNA breaks.
- Blocking protein synthesis at the ribosome.
- Depleting the cell of essential nutrients.
Answer: Causing double-strand DNA breaks.
6. What is the primary cellular target for blinatumomab?
- CD19-positive B-cell lymphoblasts
- CD22-positive T-cells
- All rapidly dividing cells
- Myeloid precursor cells
Answer: CD19-positive B-cell lymphoblasts
7. Both inotuzumab ozogamicin and blinatumomab are indicated for the treatment of:
- Chronic Myeloid Leukemia (CML)
- Advanced Hodgkin Lymphoma
- Relapsed or refractory B-cell precursor Acute Lymphoblastic Leukemia (ALL)
- Triple-negative breast cancer
Answer: Relapsed or refractory B-cell precursor Acute Lymphoblastic Leukemia (ALL)
8. The “Bi-specific” nature of blinatumomab refers to its ability to bind to:
- Two different sites on the same antigen.
- Two different antigens on two different cells (CD19 on B-cells and CD3 on T-cells).
- Both DNA and RNA.
- A receptor and its intracellular signaling partner.
Answer: Two different antigens on two different cells (CD19 on B-cells and CD3 on T-cells).
9. A key advantage of an Antibody-Drug Conjugate (ADC) like inotuzumab ozogamicin is:
- The broad, non-specific distribution of the cytotoxic agent.
- The targeted delivery of a highly potent cytotoxic agent to antigen-expressing cancer cells.
- Its oral route of administration.
- The lack of any potential for myelosuppression.
Answer: The targeted delivery of a highly potent cytotoxic agent to antigen-expressing cancer cells.
10. For a patient to be eligible for treatment with either inotuzumab or blinatumomab, their leukemia cells must:
- Be negative for all surface antigens.
- Express the appropriate B-cell antigen (CD22 or CD19).
- Have a specific kinase mutation.
- Be slow-growing.
Answer: Express the appropriate B-cell antigen (CD22 or CD19).
11. The active learning session for this topic, a “Team Debate,” likely focuses on what clinical question?
- Which agent, inotuzumab or blinatumomab, is the better option for heavily pretreated ALL.
- Whether traditional chemotherapy is superior to targeted therapy.
- The proper way to diagnose Adult ALL.
- The cost-effectiveness of these therapies.
Answer: Which agent, inotuzumab or blinatumomab, is the better option for heavily pretreated ALL.
12. The “ozogamicin” part of inotuzumab ozogamicin refers to the:
- Antibody component.
- Linker molecule.
- Cytotoxic drug payload.
- Targeting antigen.
Answer: The cytotoxic drug payload.
13. A critical step in the mechanism of an ADC is:
- The ADC remaining on the cell surface.
- The internalization of the ADC into the cancer cell.
- The release of the payload outside the target cell.
- The binding of the ADC to a T-cell.
Answer: The internalization of the ADC into the cancer cell.
14. What is the role of the CD3 receptor in the mechanism of blinatumomab?
- It is the target on the B-cell lymphoblast.
- It is an activating receptor on the surface of T-cells.
- It is a cytokine that promotes cell growth.
- It is not involved in the mechanism of blinatumomab.
Answer: It is an activating receptor on the surface of T-cells.
15. The lecture on “Adult Acute Lymphoblastic Leukemia” provides the necessary background on the:
- Disease state that these targeted therapies treat.
- Structure of monoclonal antibodies.
- Principles of non-inferiority trials.
- Management of melanoma.
Answer: Disease state that these targeted therapies treat.
16. A potential severe adverse effect associated with blinatumomab due to T-cell activation is:
- Veno-occlusive liver disease.
- Cytokine Release Syndrome (CRS).
- Severe cardiotoxicity.
- Hemorrhagic cystitis.
Answer: Cytokine Release Syndrome (CRS).
17. A boxed warning for inotuzumab ozogamicin is for what serious adverse event?
- Neurotoxicity.
- Hepatotoxicity, including veno-occlusive disease (VOD).
- Severe infusion reactions.
- Pulmonary fibrosis.
Answer: Hepatotoxicity, including veno-occlusive disease (VOD).
18. Blinatumomab is administered as a continuous intravenous infusion because:
- It has a very long half-life.
- It has a very short half-life and requires continuous exposure to be effective.
- It is an oral medication.
- This method reduces the risk of hepatotoxicity.
Answer: It has a very short half-life and requires continuous exposure to be effective.
19. The concept of “harnessing” targeted therapies implies:
- Using them as a last resort only.
- Actively using knowledge of tumor biology to select the right drug for the right patient.
- Combining all available targeted therapies for every patient.
- Avoiding the use of targeted therapies in oncology.
Answer: Actively using knowledge of tumor biology to select the right drug for the right patient.
20. The clinical trials mentioned in the syllabus reading compare inotuzumab and blinatumomab to:
- Each other directly.
- Standard therapy or conventional chemotherapy.
- A placebo.
- Best supportive care only.
Answer: Standard therapy or conventional chemotherapy.
21. A pharmacist’s role in managing a patient on blinatumomab includes monitoring for:
- Signs and symptoms of Cytokine Release Syndrome and neurotoxicity.
- High blood glucose levels.
- The development of a skin rash only.
- An increase in INR.
Answer: Signs and symptoms of Cytokine Release Syndrome and neurotoxicity.
22. Which part of an ADC provides its specificity?
- The cytotoxic payload.
- The linker.
- The monoclonal antibody component.
- The manufacturing process.
Answer: The monoclonal antibody component.
23. Blinatumomab effectively turns the patient’s own T-cells into weapons against:
- All cells in the body.
- CD19-expressing tumor cells.
- Bacterial infections.
- Viral infections.
Answer: CD19-expressing tumor cells.
24. The term “heavily pretreated ALL” implies that the patients:
- Have been newly diagnosed.
- Have failed multiple prior lines of chemotherapy.
- Are being treated in the first-line setting.
- Are not eligible for any treatment.
Answer: Have failed multiple prior lines of chemotherapy.
25. A key difference between the mechanisms of inotuzumab and blinatumomab is:
- Inotuzumab delivers a chemical toxin; blinatumomab uses the patient’s immune system.
- Blinatumomab delivers a chemical toxin; inotuzumab uses the immune system.
- Both drugs work by inhibiting kinase enzymes.
- There is no difference in their mechanisms.
Answer: Inotuzumab delivers a chemical toxin; blinatumomab uses the patient’s immune system.
26. The linker in an antibody-drug conjugate must be:
- Stable in the bloodstream but cleavable inside the target cell.
- Unstable in the bloodstream to allow for early payload release.
- Permanently attached to the payload.
- Made of a radioactive material.
Answer: Stable in the bloodstream but cleavable inside the target cell.
27. A patient with CD22-negative ALL would be a candidate for which therapy?
- Inotuzumab ozogamicin.
- Blinatumomab (if CD19-positive).
- Both inotuzumab and blinatumomab.
- Neither inotuzumab nor blinatumomab.
Answer: Blinatumomab (if CD19-positive).
28. The development of targeted therapies like these relies on identifying:
- Unique surface antigens on cancer cells that are not present on most healthy cells.
- The most potent available chemotherapy.
- The cheapest drugs to manufacture.
- Drugs with the most side effects.
Answer: Unique surface antigens on cancer cells that are not present on most healthy cells.
29. A pharmacist would need to educate the nursing staff on the specific administration requirements and potential toxicities of:
- Both inotuzumab and blinatumomab, as they are complex biologics.
- Only standard chemotherapy agents.
- Over-the-counter medications only.
- Oral targeted therapies only.
Answer: Both inotuzumab and blinatumomab, as they are complex biologics.
30. The “deep dive” mentioned in the module title implies:
- A superficial overview of the topic.
- An in-depth analysis of the mechanisms and clinical data for these specific drugs.
- A review of all leukemia treatments.
- A discussion of surgical options for ALL.
Answer: An in-depth analysis of the mechanisms and clinical data for these specific drugs.
31. The debate topic comparing inotuzumab and blinatumomab forces students to:
- Choose a side without evidence.
- Critically evaluate and compare the risk-benefit profiles of two different targeted therapies.
- Agree that both drugs are identical.
- Focus only on the cost of the medications.
Answer: Critically evaluate and compare the risk-benefit profiles of two different targeted therapies.
32. The success of targeted therapies in ALL has led to:
- The discontinuation of all chemotherapy use.
- No improvement in patient outcomes.
- Significant improvements in outcomes for patients with relapsed/refractory disease.
- A decrease in the number of new drugs being developed.
Answer: Significant improvements in outcomes for patients with relapsed/refractory disease.
33. Cytokine Release Syndrome (CRS) is managed with supportive care and may require treatment with what specific agent?
- Infliximab
- Tocilizumab (an IL-6 receptor antagonist)
- Rituximab
- High-dose chemotherapy
Answer: Tocilizumab (an IL-6 receptor antagonist)
34. A key part of harnessing targeted therapies is:
- Biomarker testing to select appropriate patients.
- Giving the therapy to all patients with the disease, regardless of markers.
- Avoiding all laboratory monitoring.
- Using the lowest possible dose to minimize efficacy.
Answer: Biomarker testing to select appropriate patients.
35. An advantage of blinatumomab’s mechanism is that it:
- Does not require the cancer cell to internalize the drug.
- Has no potential side effects.
- Is effective against all types of cancer.
- Is administered as a single oral dose.
Answer: Does not require the cancer cell to internalize the drug.
36. A pharmacist calculating the dose for blinatumomab must pay close attention to the:
- Step-up dosing schedule designed to mitigate CRS risk.
- Patient’s INR value.
- Patient’s dietary intake of vitamin K.
- Color of the patient’s eyes.
Answer: Step-up dosing schedule designed to mitigate CRS risk.
37. The clinical trial reading for inotuzumab ozogamicin likely compares its efficacy versus what?
- Blinatumomab directly.
- Standard of care chemotherapy.
- A placebo.
- An unrelated targeted therapy.
Answer: Standard of care chemotherapy.
38. The use of highly specific targeted therapies like these is a hallmark of:
- Palliative care.
- Precision medicine.
- Non-sterile compounding.
- Pharmacy informatics.
Answer: Precision medicine.
39. Management of neurotoxicity from blinatumomab may involve:
- Increasing the infusion rate.
- Withholding the drug and administering corticosteroids.
- Administering a reversal agent.
- Switching to inotuzumab immediately.
Answer: Withholding the drug and administering corticosteroids.
40. The term “Acute Lymphoblastic Leukemia” indicates that the cancer involves:
- Mature lymphocytes.
- Immature lymphoblasts.
- Myeloid cells.
- Red blood cells.
Answer: Immature lymphoblasts.
41. For an ADC to be effective, the target antigen must be:
- Present on healthy cells but not cancer cells.
- Highly expressed on cancer cells with limited expression on healthy cells.
- Secreted from the cancer cell.
- Located inside the nucleus.
Answer: Highly expressed on cancer cells with limited expression on healthy cells.
42. The “Engager” part of the BiTE acronym signifies the drug’s role in:
- Binding to DNA.
- Engaging the patient’s T-cells to attack cancer cells.
- Engaging in protein synthesis.
- Engaging with a second chemotherapy agent.
Answer: Engaging the patient’s T-cells to attack cancer cells.
43. A pharmacist reviewing a patient’s lab work before they receive inotuzumab ozogamicin would be most concerned with:
- Serum sodium levels.
- Liver function tests (LFTs) and bilirubin.
- Hemoglobin A1c.
- Lipid panel.
Answer: Liver function tests (LFTs) and bilirubin.
44. The development of therapies like inotuzumab and blinatumomab was made possible by advances in:
- Monoclonal antibody technology.
- Oral drug formulation.
- Small molecule synthesis.
- Computer programming.
Answer: Monoclonal antibody technology.
45. Which therapy works by directly delivering a poison to the cancer cell?
- Blinatumomab.
- Nivolumab.
- Inotuzumab ozogamicin.
- Standard chemotherapy.
Answer: Inotuzumab ozogamicin.
46. A patient with a history of liver disease would be at higher risk for toxicity with which agent?
- Blinatumomab.
- Inotuzumab ozogamicin.
- Both are equally risky for the liver.
- Neither poses a risk to the liver.
Answer: Inotuzumab ozogamicin.
47. A primary role for the pharmacist when a patient is receiving continuous infusion blinatumomab is:
- Ensuring the correct infusion rate and managing the administration logistics.
- Performing daily blood draws.
- Counseling the patient on a low-sodium diet.
- Compounding the drug into an oral liquid.
Answer: Ensuring the correct infusion rate and managing the administration logistics.
48. Both inotuzumab and blinatumomab target antigens on B-lineage cells. A predictable consequence of this is:
- An increase in the number of B-cells.
- B-cell aplasia (depletion of B-cells).
- No effect on the B-cell count.
- A specific increase in T-cell count.
Answer: B-cell aplasia (depletion of B-cells).
49. An understanding of these targeted therapies is essential for a pharmacist specializing in:
- Community pharmacy.
- Nuclear pharmacy.
- Hematology/Oncology.
- Nutrition support.
Answer: Hematology/Oncology.
50. The ultimate goal of harnessing targeted therapies is to:
- Increase treatment toxicity and cost.
- Improve efficacy and reduce toxicity compared to non-specific chemotherapy.
- Make cancer treatment more complicated.
- Eliminate the need for supportive care medications.
Answer: Improve efficacy and reduce toxicity compared to non-specific chemotherapy.
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
Mail- Sachin@pharmacyfreak.com