MCQ Quiz: Personalized Medicine – Transplantation

Personalized medicine is revolutionizing the field of solid organ transplantation by moving beyond a one-size-fits-all approach to immunosuppression. By leveraging tools like pharmacogenomics (PGx), immunologic testing, and therapeutic drug monitoring (TDM), clinicians can tailor drug therapy to an individual patient’s genetic makeup and immune profile. This strategy aims to optimize drug efficacy, minimize the risk of organ rejection, and reduce drug-related toxicities. For the transplant pharmacist, interpreting and applying this data is a critical skill. This quiz is designed for PharmD students to test their knowledge on the application of personalized medicine principles, with a key focus on the pharmacogenomics of tacrolimus and the role of genetic testing in optimizing transplant outcomes.

1. What is the primary goal of personalized medicine in solid organ transplantation?

• a) To use the same dose of medication for every patient.
• b) To increase the number of organ rejections.
• c) To tailor immunosuppressive therapy to an individual to maximize efficacy and minimize toxicity.
• d) To eliminate the need for therapeutic drug monitoring.

Answer: c) To tailor immunosuppressive therapy to an individual to maximize efficacy and minimize toxicity.

2. The pharmacogenomic testing of which gene is most clinically relevant for personalizing the dose of tacrolimus?

• a) TPMT
• b) VKORC1
• c) CYP2C19
• d) CYP3A5

Answer: d) CYP3A5

**3. A patient with a CYP3A5 1/1 genotype is known as a:

• a) Poor metabolizer of tacrolimus.
• b) Intermediate metabolizer of tacrolimus.
• c) Extensive (or Normal) metabolizer of tacrolimus.
• d) Non-metabolizer of tacrolimus.

Answer: c) Extensive (or Normal) metabolizer of tacrolimus.

4. How does the CYP3A5 genotype impact tacrolimus dosing requirements?

• a) CYP3A5 expressers (*1/*1 or *1/*3) require significantly higher doses of tacrolimus to achieve therapeutic trough levels.
• b) CYP3A5 expressers require lower doses of tacrolimus.
• c) The CYP3A5 genotype has no effect on tacrolimus dosing.
• d) It only affects cyclosporine dosing.

**Answer: a) CYP3A5 expressers (*1/*1 or 1/3) require significantly higher doses of tacrolimus to achieve therapeutic trough levels.

5. The most common non-functional allele for the CYP3A5 gene, leading to a non-expresser or poor metabolizer phenotype, is:

• a) CYP3A5 *1
• b) CYP3A5 *2
• c) CYP3A5 *3
• d) CYP3A5 *4

*Answer: c) CYP3A5 3

*6. The frequency of the CYP3A5 1 (expresser) allele is highest in which population, leading to higher tacrolimus dose requirements on average?

• a) Individuals of European ancestry.
• b) Individuals of African ancestry.
• c) Individuals of East Asian ancestry.
• d) The frequency is the same across all populations.

Answer: b) Individuals of African ancestry.

7. According to the Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines, what is the recommendation for a known CYP3A5 expresser starting tacrolimus?

• a) Start with a standard dose.
• b) Start with a lower-than-standard dose.
• c) Start with a 1.5 to 2 times higher-than-standard dose, followed by TDM.
• d) Avoid the use of tacrolimus.

Answer: c) Start with a 1.5 to 2 times higher-than-standard dose, followed by TDM.

8. Therapeutic Drug Monitoring (TDM) of tacrolimus trough levels is a form of personalized medicine because it:

• a) Allows for dose adjustments based on an individual’s measured drug exposure.
• b) Eliminates the need for genetic testing.
• c) Is only done once after transplant.
• d) Measures the function of the transplanted organ.

Answer: a) Allows for dose adjustments based on an individual’s measured drug exposure.

9. A patient’s tacrolimus dose was recently increased, but their trough level remains subtherapeutic. Before increasing the dose further, the pharmacist should first assess:

• a) The patient’s blood type.
• b) The patient’s medication adherence.
• c) The patient’s HLA type.
• d) The cost of the medication.

Answer: b) The patient’s medication adherence.

10. Pharmacogenomic testing for TPMT or NUDT15 is essential before starting which immunosuppressant to avoid severe myelosuppression?

• a) Tacrolimus
• b) Cyclosporine
• c) Azathioprine
• d) Prednisone

Answer: c) Azathioprine

11. Human Leukocyte Antigen (HLA) matching is a form of personalized medicine that aims to:

• a) Match the size of the donor organ to the recipient.
• b) Minimize the immunologic differences between the donor and recipient to reduce rejection risk.
• c) Determine the correct dose of immunosuppressants.
• d) Predict the risk of post-transplant infections.

Answer: b) Minimize the immunologic differences between the donor and recipient to reduce rejection risk.

12. A high Panel Reactive Antibody (PRA) percentage indicates that a transplant candidate:

• a) Has a very low risk of rejection.
• b) Is highly sensitized and has pre-formed antibodies against a large portion of the donor population.
• c) Will not require immunosuppression.
• d) Is a universal recipient.

Answer: b) Is highly sensitized and has pre-formed antibodies against a large portion of the donor population.

13. What is the purpose of a crossmatch test performed just before transplantation?

• a) To confirm the patient’s blood type.
• b) To determine the tacrolimus dose.
• c) To detect the presence of pre-formed, donor-specific antibodies (DSAs) in the recipient’s serum.
• d) To check for active infections.

Answer: c) To detect the presence of pre-formed, donor-specific antibodies (DSAs) in the recipient’s serum.

14. A positive crossmatch test typically means:

• a) The transplant can proceed without any issues.
• b) The risk of hyperacute rejection is very high, and the transplant is generally not performed.
• c) The patient will require lower doses of immunosuppression.
• d) The patient has a perfect HLA match with the donor.

Answer: b) The risk of hyperacute rejection is very high, and the transplant is generally not performed.

15. Monitoring for de novo Donor-Specific Antibodies (DSAs) after transplant is a personalized approach to:

• a) Assess for medication adherence.
• b) Identify patients at higher risk for antibody-mediated rejection.
• c) Check for CMV infection.
• d) Determine the patient’s CYP3A5 genotype.

Answer: b) Identify patients at higher risk for antibody-mediated rejection.

**16. A patient with a CYP3A5 3/3 genotype is a tacrolimus poor metabolizer. This patient will likely:

• a) Require a much higher dose of tacrolimus.
• b) Achieve therapeutic levels with a standard or lower-than-standard dose of tacrolimus.
• c) Be unable to absorb tacrolimus orally.
• d) Experience severe nephrotoxicity regardless of the dose.

Answer: b) Achieve therapeutic levels with a standard or lower-than-standard dose of tacrolimus.

17. What is the pharmacist’s primary responsibility when they receive a patient’s CYP3A5 genotype result?

• a) To perform the transplant surgery.
• b) To use the result to recommend an initial or adjusted tacrolimus dose according to clinical guidelines.
• c) To keep the result confidential from the transplant team.
• d) To order more genetic tests.

Answer: b) To use the result to recommend an initial or adjusted tacrolimus dose according to clinical guidelines.

18. Some studies suggest that genetic variations in UGT1A9 can affect the metabolism of which immunosuppressant?

• a) Tacrolimus
• b) Mycophenolic acid (MPA)
• c) Prednisone
• d) Sirolimus

Answer: b) Mycophenolic acid (MPA)

19. The concept of using biomarkers (e.g., gene expression profiles from a biopsy) to differentiate between types of rejection is an example of:

• a) Therapeutic drug monitoring.
• b) Standardized medicine.
• c) Personalized diagnostics.
• d) Prophylactic therapy.

Answer: c) Personalized diagnostics.

20. A transplant recipient who is a CYP3A4 poor metabolizer (due to genetics or interacting drugs) would likely require a __________ dose of tacrolimus.

• a) higher
• b) lower
• c) loading
• d) weekly

Answer: b) lower

21. A patient with a TPMT poor metabolizer phenotype is prescribed a standard dose of azathioprine. This puts them at extremely high risk for:

• a) Nephrotoxicity
• b) Life-threatening myelosuppression (severe leukopenia).
• c) Hyperglycemia
• d) Acute rejection

Answer: b) Life-threatening myelosuppression (severe leukopenia).

22. “Personalized” induction therapy might involve choosing antithymocyte globulin (a potent, depleting agent) over basiliximab for a patient who is:

• a) At very low immunologic risk.
• b) EBV-negative.
• c) At very high immunologic risk (e.g., highly sensitized with a high PRA).
• d) A perfect HLA match with the donor.

Answer: c) At very high immunologic risk (e.g., highly sensitized with a high PRA).

23. The development of cell-free DNA (cfDNA) blood tests is an emerging personalized medicine tool used to:

• a) Determine a patient’s CYP3A5 genotype.
• b) Non-invasively monitor for organ rejection by detecting donor-derived DNA in the recipient’s blood.
• c) Measure tacrolimus levels.
• d) Screen for post-transplant diabetes.

Answer: b) Non-invasively monitor for organ rejection by detecting donor-derived DNA in the recipient’s blood.

24. A pharmacist notes that a patient who is a CYP3A5 expresser has consistently subtherapeutic tacrolimus levels despite reporting good adherence. This finding may prompt the pharmacist to:

• a) Recommend switching to cyclosporine.
• b) Recommend a higher or more frequent tacrolimus dose and continue TDM.
• c) Accuse the patient of being non-adherent.
• d) Stop monitoring tacrolimus levels.

Answer: b) Recommend a higher or more frequent tacrolimus dose and continue TDM.

25. A key limitation of relying solely on pre-emptive CYP3A5 genotyping for tacrolimus dosing is that:

• a) It is not a clinically validated test.
• b) It is too expensive to be useful.
• c) Many other clinical and genetic factors also influence tacrolimus levels, so TDM is still essential.
• d) The results take months to come back.

Answer: c) Many other clinical and genetic factors also influence tacrolimus levels, so TDM is still essential.

26. A patient is prescribed cyclosporine. Unlike tacrolimus, its metabolism is primarily dependent on which enzyme, making CYP3A5 genotype less predictive?

• a) CYP2C9
• b) CYP2D6
• c) CYP3A4
• d) TPMT

Answer: c) CYP3A4

27. A personalized approach to managing CMV risk involves:

• a) Treating all patients with the same dose and duration of valganciclovir.
• b) Tailoring the strategy (prophylaxis vs. pre-emptive therapy) and duration based on donor/recipient serostatus.
• c) Using only non-pharmacologic methods.
• d) Ignoring CMV status.

Answer: b) Tailoring the strategy (prophylaxis vs. pre-emptive therapy) and duration based on donor/recipient serostatus.

28. A potential future application of personalized medicine in transplant is using genetic markers to predict a patient’s risk of developing:

• a) CNI-induced nephrotoxicity.
• b) New-onset diabetes after transplantation (NODAT).
• c) Specific opportunistic infections.
• d) All of the above.

Answer: d) All of the above.

29. A patient is taking voriconazole (a strong CYP3A4/3A5 inhibitor) and tacrolimus. What dose adjustment is needed for tacrolimus?

• a) No adjustment is needed.
• b) A significant dose increase is required.
• c) A significant dose reduction is required, often by 50-75%.
• d) Tacrolimus should be switched to sirolimus.

Answer: c) A significant dose reduction is required, often by 50-75%.

30. The field of pharmacometabolomics in transplantation aims to:

• a) Study the genetic basis of drug metabolism.
• b) Measure drug levels in the blood.
• c) Analyze small-molecule metabolites to identify biomarkers of drug response or toxicity.
• d) Develop new immunosuppressant drugs.

Answer: c) Analyze small-molecule metabolites to identify biomarkers of drug response or toxicity.

31. The primary barrier to the widespread implementation of routine pharmacogenomic testing in transplantation is:

• a) Lack of clinical guidelines.
• b) The tests are not scientifically valid.
• c) Cost, logistics, and the time to get results in the acute transplant setting.
• d) The results do not provide any useful information.

Answer: c) Cost, logistics, and the time to get results in the acute transplant setting.

**32. A patient has a CYP3A5 1/3 genotype. This patient is considered a(n):

• a) Poor metabolizer.
• b) Intermediate metabolizer.
• c) Extensive (Normal) metabolizer.
• d) Ultrarapid metabolizer.

Answer: b) Intermediate metabolizer.

33. What is the role of TDM in personalizing mycophenolate therapy?

• a) It is a standard of care for all patients.
• b) It is not useful because there is no correlation between drug levels and outcomes.
• c) It is not routinely done, but may be considered in cases of rejection or severe toxicity to assess exposure.
• d) Trough levels are measured daily.

Answer: c) It is not routinely done, but may be considered in cases of rejection or severe toxicity to assess exposure.

34. The ultimate goal of using personalized medicine approaches like PGx and TDM is to improve:

• a) Pharmacy revenue.
• b) The number of transplants performed.
• c) Long-term graft survival and patient quality of life.
• d) The speed of the transplant operation.

Answer: c) Long-term graft survival and patient quality of life.

35. A “virtual crossmatch” is a form of personalized medicine that:

• a) Involves mixing donor and recipient serum in a lab.
• b) Uses a computer algorithm to predict the immunologic risk by comparing the recipient’s known antibodies to the donor’s HLA type.
• c) Is used to determine tacrolimus levels.
• d) Is a type of video game for transplant candidates.

Answer: b) Uses a computer algorithm to predict the immunologic risk by comparing the recipient’s known antibodies to the donor’s HLA type.

36. A transplant pharmacist using a patient’s genetic information to guide therapy is practicing at the intersection of pharmacotherapy and:

• a) Surgery
• b) Informatics
• c) Genomics
• d) Both B and C

Answer: d) Both B and C

37. Which of the following immunosuppressants has its metabolism LEAST affected by CYP3A5 genotype?

• a) Tacrolimus
• b) Sirolimus
• c) Mycophenolate mofetil
• d) Everolimus

Answer: c) Mycophenolate mofetil

38. Tailoring the type of induction therapy (e.g., ATG vs. basiliximab) based on a patient’s immunologic risk profile is an example of:

• a) TDM
• b) PGx
• c) Personalized medicine
• d) A medication error

Answer: c) Personalized medicine

39. If a patient who is stable on tacrolimus is started on rifampin (a strong CYP3A4/3A5 inducer), what is the expected impact on their tacrolimus trough level?

• a) A significant increase.
• b) No change.
• c) A significant decrease, potentially leading to rejection.
• d) A slight, clinically insignificant decrease.

Answer: c) A significant decrease, potentially leading to rejection.

40. A patient’s personalized medicine profile includes being a CYP3A5 non-expresser and having a low PRA. This patient would likely:

• a) Require high-dose induction and high maintenance tacrolimus doses.
• b) Be at very high immunologic risk.
• c) Require standard or lower-than-standard tacrolimus doses and may be a candidate for less potent induction.
• d) Be ineligible for transplantation.

Answer: c) Require standard or lower-than-standard tacrolimus doses and may be a candidate for less potent induction.

41. The use of allograft-derived cell-free DNA as a biomarker represents a personalized approach to:

• a) Dosing medications.
• b) Preventing infections.
• c) Monitoring for rejection non-invasively.
• d) Assessing medication adherence.

Answer: c) Monitoring for rejection non-invasively.

42. Which factor is NOT typically considered part of a personalized medicine approach in transplant?

• a) Pharmacogenomics
• b) Patient’s zodiac sign
• c) Donor-specific antibody status
• d) Therapeutic drug monitoring

Answer: b) Patient’s zodiac sign

43. A key benefit of pre-transplant pharmacogenomic testing for CYP3A5 is the ability to:

• a) Eliminate the risk of rejection.
• b) Achieve therapeutic tacrolimus levels more quickly after transplant.
• c) Avoid the need for TDM.
• d) Guarantee long-term graft survival.

Answer: b) Achieve therapeutic tacrolimus levels more quickly after transplant.

44. A patient has a genetic variant that leads to increased expression of P-glycoprotein (an efflux transporter) in the gut. How might this affect the absorption of an oral CNI like tacrolimus?

• a) It would increase absorption, leading to higher levels.
• b) It would decrease absorption, leading to lower levels.
• c) It would have no effect on absorption.
• d) It would slow down the metabolism of the drug.

Answer: b) It would decrease absorption, leading to lower levels.

45. Personalized medicine aims to shift the paradigm of treatment from a __________ approach to a more tailored one.

• a) Reactive
• b) Proactive
• c) Historical
• d) Financial

Answer: a) Reactive

46. If a hospital pharmacy implements a protocol to dose tacrolimus based on CYP3A5 genotype, who is the key professional responsible for interpreting the results and recommending the dose?

• a) The surgeon
• b) The nurse
• c) The pharmacist
• d) The lab technician

Answer: c) The pharmacist

47. A “drug holiday” from mycophenolate due to leukopenia is a reactive measure. A personalized medicine approach might involve:

• a) Ignoring the low white blood cell count.
• b) Proactively screening for gene variants (like in UGT) that might predict toxicity.
• c) Always using the maximum dose of mycophenolate.
• d) Discontinuing the drug permanently.

Answer: b) Proactively screening for gene variants (like in UGT) that might predict toxicity.

48. Why is achieving the target tacrolimus trough level quickly important in the early post-transplant period?

• a) To minimize the cost of the medication.
• b) To reduce the risk of acute rejection, which is highest during this time.
• c) To prevent long-term side effects.
• d) To allow the patient to be discharged faster.

Answer: b) To reduce the risk of acute rejection, which is highest during this time.

49. The future of personalized medicine in transplantation may include:

• a) Using artificial intelligence to predict rejection risk based on multiple data points.
• b) Developing a “tolerance” score to identify patients who may be able to wean off immunosuppression.
• c) Using microbiome analysis to predict infection risk.
• d) All of the above.

Answer: d) All of the above.

50. The ultimate clinical utility of any personalized medicine tool (e.g., a genetic test) is determined by whether it:

• a) Is new and technologically advanced.
• b) Is expensive.
• c) Leads to a change in management that improves patient outcomes.
• d) Is easy to perform.

Answer: c) Leads to a change in management that improves patient outcomes.