Case Study 9

For each question, choose the answer you think is correct. Answers are provided at the end of the page.
​​​​​​​​​​​​​​​​​​​​​​S.M. is a 70-year-old female diagnosed with resectable stage III​ melanoma,  BRAF mutation positive. Given her age and comorbidities, she was deemed to be a candidate for the SMNAIPNI protocol.

Lab results taken 24 hours prior to first treatment:
Lab value
 Patient's labs
 Normal range 
WBC
5.5
4 – 10 x 109/L
ANC
3.2
2 – 7.5 x 109/L
Hgb
125
115 – 155 g/L
Plt
349
150 – 400 x 109/L
SCr
71
45 – 90 µmol/L​
eGFR
75
≥ 60 mL/min/1.73m2
TSH
0.36
0.32 – 5.04 mU/L
AM Cortisol
250
125 – 536 nmol/L
AST
6
<36 U/L
ALT
8
<36 U/L
ALP
77
35 – 120 U/L
Total bilirubin
6
<17 µmol/L​​​
LDH
148
<225 U/L

Weight = 62.1 kg, Height = 160 cm

1. Which of the following best describes the BC Cancer benefit status of nivolumab and ipilimumab in this protocol?

  1. They are Class I drugs and do not require special approval prior to treatment
  2. They are Class I drugs and special approval must be obtained prior to treatment
  3. They are restricted drugs but do not require special approval prior to treatment
  4. They are restricted drugs and case-by-case Compassionate Access Program (CAP) approval must be obtained prior to treatment

2. Which of the following would be the most appropriate doses of nivolumab and ipilimumab for S.M.?

  1. 5.76 mg nivolumab and 1.92 mg ipilimumab
  2. 576 mg nivolumab and 192 mg ipilimumab
  3. 240 mg nivolumab and 80 mg ipilimumab
  4. 249 mg nivolumab and 83 mg ipilimumab

3. Which pre-medications should S.M. receive prior to her first dose of nivolumab and ipilimumab?

  1. diphenhydrAMINE 50 mg PO 30 minutes prior to treatment
  2. acetaminophen 325 - 975 mg PO 30 minutes prior to treatment
  3. hydrocortisone 25 mg IV 30 minutes prior to treatment
  4. All of the above
  5. None of the above

4. Which of the following best describes the safe handling precautions for nivolumab and ipilimumab?

  1. They are not hazardous drugs and should be mixed by the RN in the treatment room
  2. They are not hazardous drugs but should be mixed in pharmacy as per local standards of non-hazardous drug sterile compounding
  3. They are not hazardous drugs and should be mixed in pharmacy as per local standards of hazardous drug sterile compounding
  4. They are biohazardous drugs and extreme precautions should be taken in pharmacy when compounding

5.  As both nivolumab and ipilimumab are monoclonal antibodies, can they be given through a Y-site? 

  1. Yes, both nivolumab and ipilimumab can be given through a Y-site once prepared by pharmacy
  2. Yes, both nivolumab and ipilimumab can be given through a Y-site but one 0.2 micron in-line filter is required after the Y-site 
  3. Yes, both nivolumab and ipilimumab can be given through a Y-site once prepared by pharmacy, as long as two separate 0.2 micron in-line filters are used before the Y-site
  4. No, both nivolumab and ipilimumab require a separate infusion line and a separate 0.2 micron in-line filter

​6. How often and how many cycles of this protocol can be given prior to surgery?

  1. Treatment is given every week for 3 cycles unless disease progression during treatment or unacceptable toxicity
  2. Treatment is given every 2 weeks for 3 cycles unless disease progression during treatment or unacceptable toxicity
  3. Treatment is given every 3 weeks for 2 cycles unless disease progression during treatment or unacceptable toxicity
  4. Treatment is given every 2 weeks indefinitely unless disease progression during treatment or unacceptable toxicity

​7. On the day of her 2nd cycle of SMNAIPNI, S.M. calls the clinic reporting 4 to 6 loose bowel movements per day over the past few days (baseline was 1 per day). She has been taking loperamide without improvement and reports intermittent abdominal pain. What would you recommend?

  1. ​Proceed with nivolumab and ipilimumab treatment today as planned, at the same dose
  2. Proceed with nivolumab and ipilimumab treatment today as planned, but at a reduced dose
  3. Hold nivolumab and ipilimumab treatment today and have her physician assess for immune-related enterocolitis, which may require treatment with oral corticosteroids (e.g., prednisone)
  4. Hold nivolumab and ipilimumab treatment today and have her physician assess for immune-related enterocolitis, which may require treatment with antibiotics (e.g., vancomycin)

​8. S.M.’s diarrhea has now resolved. However, she has lost weight following the episode and now weighs 76 kg. Her prescribed doses remain the same. How would you proceed?

  1. ​Proceed with treatment as planned, as the new weight change is not clinically significant and does not result in a clinically significant dose variance
  2. Discuss with the prescriber whether dose recalculation is needed, as the new weight results in a dose variance greater than 5% 
  3. Discuss with the prescriber whether dose recalculation is needed, as the patient’s weight has changed by more than 10% from baseline
  4. Discuss with the prescriber whether dose recalculation is needed, as the new weight results in a dose variance greater than 10%

9. S.M. returns after complete surgical resection but was found to have only a partial pathological response. She is found to be BRAF wild-type. What should be her next line of treatment?

  1. Continue SMNAIPNI every 3 weeks until progression or toxicity
  2. Give adjuvant nivolumab (SMAJNIV4) for an additional 11 cycles (every 4 weeks) or complete adjuvant phase with pembrolizumab using SMNAPEM
  3. Give oral dabrafenib and oral trametinib (SMAJDT) for an additional 11 cycles of adjuvant treatment
  4. She is now considered palliative and should receive only supportive management of her symptoms

​10. ​​S.M. returns after her 8th cycle of adjuvant nivolumab for assessment. Her labs done yesterday show TSH <0.1 mU/L (second cycle in a row) and a free T4 that is high. She also reports experiencing palpitations, heat intolerance and increased fatigue that is affecting her daily life activities. How would you proceed?

  1. ​Hold nivolumab treatment today and have her physician assess for immune-related endocrine hyperthyroidism and/or graves disease
  2. Refer her for endocrinology assessment
  3. Assess if she requires a beta blocker for symptom control
  4. All of the above
 


 


 
 
The correct answer is 3.

Rationale: Based on her symptoms, S.M. is experiencing Grade 2 diarrhea which has not resolved despite antidiarrheal treatment. According to the Enterocolitis chart located at the end of the SCIMMUNE protocol, ipilimumab should be withheld until her symptoms resolve to Grade 1 or lower. She should also be assessed to rule out any infectious etiology, and may need to be started on immunosuppressive corticosteroid treatment with predniSONE 0.5 to 1 mg/kg/day PO if the problem persists beyond 3 to 5 days or recurs.

Answer 1
​The correct answer is 1.

Rationale: According to the BC Cancer Benefit Drug List, ipilimumab and nivolumab are both Class I drugs when used for the listed indication.

Answer 2
​​The correct answer is 3.

Rationale: Ipilimumab and nivolumab dosing is calculated using weight and not BSA. According to the SMNAIPNI protocol, nivolumab 3 mg/kg and ipilimumab 1 mg/kg doses should be calculated and then dose banded using the provided dose banding tables. After calculation, doses are nivolumab 249 mg and ipilimumab 83 mg. However, the protocol caps doses at nivolumab 240 mg and ipilimumab 80 mg and there is no dose banding information above these maximum allowed doses. Therefore, the final dose for nivolumab is 240 mg and ipilimumab is 80 mg. 

Answer 3
​The correct answer is 5.

Rationale: According to the SMNAIPNI PPPO and protocol, options 1, 2, and 3 are required only in the case of a prior infusion reaction. They are not required prior to a first dose of ipilimumab and nivolumab.

Answer 4

​​The correct answer is 2.

Rationale: According to the BC Provincial Hazardous Drug List​, ipilimumab and nivolumab are not considered hazardous drugs and therefore can be prepared as per local standards of sterile non-hazardous drug compounding.​

Answer 5

​The correct answer is 4.

Rationale: According to the treatment section of SMNAIPNI protocol and PPPO, both drugs should be given using a separate infusion line and a separate 0.2 micron in-line filter for each drug.

Answer 6
The correct answer is 3.

Rationale: According to the treatment section of SMNAIPNI protocol, this treatment is repeated every 3 weeks for 2 cycles unless there is disease progression during treatment or unacceptable toxicity, followed by a total lymph node dissection (TLND) and if applicable, resection of in-transit metastases.

Answer 7
​The correct answer is 3.

Rationale: Based on her symptoms, S.M. is experiencing Grade 2 diarrhea which has not resolved despite antidiarrheal treatment. According to the Enterocolitis flowchart located at the end of the SCIMMUNE protocol, both ipilimumab and nivolumab should be withheld until her symptoms resolve to Grade 1 or lower. She should also be assessed to rule out any infectious etiology and may need to be started on immunosuppressive corticosteroid treatment with prednisone 1 mg/kg/day PO if the problem persists beyond 1 to 2 days or recurs. 

Answer 8
​The correct answer is 1.

Rationale: As per Policy III-10 update in June 2025, if a patient’s weight change results in a dose variance of greater than 10% for select monoclonal antibody drugs, even if that weight change is less than 10%, the pharmacist must contact the prescriber to discuss the dose. In this case the weight change is not greater than 10% and it also does not result in a dose variance of greater than 10%.

Answer 9
​The correct answer is 2.

Rationale: According to the treatment section of the SMNAIPNI protocol, further adjuvant treatment is guided by pathological response and BRAF mutation status. S.M. had a partial response and is BRAF wild-type. Therefore, her next line of treatment should be with adjuvant nivolumab (SMAJNIV4) for an additional 11 cycles (preferred option), or completion of adjuvant phase with pembrolizumab using SMNAPEM. 

Although S.M. received complete surgical resection, her pathology showed only partial pathological response with residual viable melanoma present after neoadjuvant checkpoint inhibitor therapy. This puts her at higher risk of recurrence and continued checkpoint inhibitor therapy is indicated to treat potential residual microscopic disease.

Answer 10
​The correct answer is 4.

Rationale: According to the supportive care protocol SCIMMUNE, “Endocrine: Hyperthyroidism” section, a patient who is symptomatic and has TSH less than 0.5 x LLN or consistently out of range in two consecutive measurements may be experiencing Grade 2 toxicities. Therefore, she will require an endocrine consultation, beta blocker for symptom control and if required, treatment for graves disease. Consider withholding checkpoint inhibitors while these investigations are being carried out.​
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