Background: Nivolumab was recently approved for a new flat-dose schedule 480 mg IV every 4 weeks (“480 Q4w”) using data from pharmacokinetics simulations without being first tested directly in humans. We noted several unusual adverse drug reactions (ADRs) using the new dosing and hypothesized that this new dose schedule might generate more ADRs than prior dosing schedules.
Methods: This study attempts to summarize and characterize the types of ADRs seen on the new 480 Q4w dosing. We conducted a retrospective, descriptive chart review and case series including patients at the San Antonio VA Hematology/Oncology clinic treated with at least one dose of Nivolumab 480 mg between 2/1/18 and 10/1/18. We tracked whether these patients developed ADRs, and if so, the highest CTCAE 4.03 grade of reaction, the number of treatments before the reaction developed, and whether the reaction influenced treatment (hold treatment, stop treatment, dose change).
Results: 18 patients matched this criterion (all male, average age 67.6 years). 6 patients experienced an ADR during treatment with the 480 Q4w dose. Grade 1 toxicities included pruritis, abdominal pain, skin rash, fatigue, fever, cramping, myalgia, and diarrhea. There was a Grade 3 case of encephalopathy and a Grade 2 case of diplopia. Of the 6 patients who experienced an adverse drug reaction, 2 (with only Grade 1 toxicities) continued treatment at their same dose frequency; the others changed to 240 mg Q2w. All 4 patients who experienced an ADR and had their dose changed to 240 mg Q2w experienced resolution or improvement in their symptoms except for 1 patient’s complaint of abdominal pain.
Conclusion: 480 Q4w dosing of Nivolumab may have a different ADR profile from prior dose regimens; further quantitative analysis will be required to answer this question. Dose frequency change may present an opportunity to relieve toxicities while allowing patients to continue treatment.
