Case Studies for Transitioning from IV to SubQ anti-PD-1

Best answer: (A) The FDA approved nivolumab and hyaluronidase-nvhy (Opdivo Qvantig) in December 2024 for subcutaneous injection across approved adult solid tumor nivolumab indications, including as monotherapy maintenance following completion of IV nivolumab plus ipilimumab combination therapy in unresectable or metastatic melanoma. Importantly, Opdivo Qvantig is not approved for concurrent use with IV ipilimumab. It may only be substituted for IV nivolumab during the monotherapy phase.¹

This patient has completed his 4-cycle induction and is now entering the maintenance monotherapy phase, making him an appropriate candidate for the switch. His prior grade 2 transaminitis, which has resolved, does not preclude the transition; the immune-related adverse event profile of SC nivolumab is comparable to IV nivolumab.

The NCCN Cutaneous Melanoma Guidelines state that nivolumab and hyaluronidase-nvhy SC injection may be substituted for IV nivolumab, noting that it has different dosing and administration instructions compared to IV nivolumab.²

The medical oncologist discusses the option of SC nivolumab with the patient. Before making a final decision, the patient wants to understand the practical differences between the two formulations.

Best answer: (C) SC nivolumab reduces administration time from 30–60 minutes to less than 5 minutes and eliminates the need for IV access.

Rationale: In the phase I/II CheckMate 8KX study, the mean duration of SC nivolumab injection was less than 5 minutes, compared with the 30-minute IV infusion plus additional time for IV line placement, flushing, and post-infusion monitoring.³

In the phase I/II CheckMate 8KX study, the mean duration of SC nivolumab injection was less than 5 minutes, compared with the 30-minute IV infusion plus additional time for IV line placement, flushing, and post-infusion monitoring.³

The phase III CheckMate 67T trial demonstrated pharmacokinetic noninferiority and comparable objective response rates between SC and IV nivolumab, with no new safety signals.⁴

A systematic review and meta-analysis of SC versus IV PD-1/PD-L1 inhibitors across 1,243 patients confirmed no significant differences in overall survival, progression-free survival, objective response rate, or adverse events between the two routes.⁵

SC administration does not eliminate clinic visits entirely. Patients still require periodic monitoring, laboratory assessments, and clinical evaluations, but it substantially reduces chair time and eliminates the need for venipuncture for drug delivery. For this patient with difficult IV access and significant time constraints, these are clinically meaningful benefits. Patient preference studies consistently show that the majority of patients prefer SC over IV delivery, citing convenience, reduced venipunctures, and shorter visits as major advantages.

The oncologist decides to transition the patient to SC nivolumab and hyaluronidase-nvhy 1,200 mg/20,000 units every 4 weeks. At his first SC administration visit, the nurse administers the injection in approximately 3–5 minutes. He is monitored briefly and discharged. He reports high satisfaction at his follow-up visit, noting that the entire clinic visit took under 45 minutes compared to his previous 4–5 hour visits for IV infusion.

Best answer: (C) SC nivolumab offers comparable pharmacokinetics, efficacy, and safety to IV nivolumab while reducing administration time, eliminating IV access requirements, and improving patient convenience.

Rationale:The rationale for favoring SC nivolumab in appropriate candidates rests on several converging lines of evidence:

• Pharmacokinetic noninferiority: The phase III CheckMate 67T trial demonstrated that SC nivolumab met predefined noninferiority thresholds for both time-averaged serum concentration and trough concentration at steady state compared to IV nivolumab⁴
• Comparable efficacy: Objective response rates were noninferior (24.2% SC vs. 18.2% IV), and additional efficacy measures were similar between arms.4⁴
• Similar safety profile: No new safety signals were observed. The incidence and severity of immune-related adverse events were comparable. Local injection site reactions with SC were mild (grade 1–2) and mostly self-resolving.⁴
• Dramatically reduced administration time: SC injection takes less than 5 minutes versus 30+ minutes for IV infusion, with additional time savings from eliminating IV line placement, flushing, and extended post-infusion monitoring.⁴
• Elimination of IV access challenges: For patients with poor venous access, a common problem in cancer patients who have undergone multiple cycles of therapy, SC administration removes a significant source of discomfort and procedural delay.
• Patient preference: In CheckMate 8KX, patients preferred SC delivery over IV or had no preference.³ A crossover study of SC versus IV pembrolizumab found that 65% of patients preferred SC, with the most common reason being less time in clinic.⁶
• Health system benefits: SC administration reduces infusion chair occupancy, nursing time, and pharmacy preparation burden, optimizing infusion center capacity.

While SC nivolumab achieves higher absolute drug exposure than IV nivolumab (geometric mean ratio of ~2.0 for time-averaged concentration), this is within the established safe therapeutic window and does not translate to clinically meaningful differences in efficacy or toxicity.5 SC nivolumab should not replace IV nivolumab during the combination phase with ipilimumab, as it is not approved for concurrent use with ipilimumab.

Best answer: (A) Yes. The reduced visit time and elimination of IV access would significantly benefit this patient and her caregiver.

Rationale:This patient is an excellent candidate for the SC switch. SC nivolumab is administered by a healthcare professional in the clinic. It does not require the patient to self-administer, so her mild cognitive impairment is not a barrier. The reduced administration time (under 5 minutes versus 30+ minutes for IV) and elimination of IV line placement would meaningfully decrease the burden on both the patient and her caregiver-daughter. BRAF mutation status does not affect eligibility for SC nivolumab. Operational studies confirm that SC administration shortens treatment delivery and reduces chair occupancy, which is particularly impactful for patients traveling long distances.

Best answer: (B) No. Opdivo Qvantig is not approved for concurrent use with IV ipilimumab; the switch can only occur after completing the combination induction phase.

Rationale:This is a critical distinction. The FDA approval and NCCN Guidelines explicitly state that nivolumab and hyaluronidase-nvhy is not approved for concurrent use with IV ipilimumab. The SC formulation may only be substituted for IV nivolumab during the monotherapy maintenance phase, that is, after the patient has completed the ipilimumab/nivolumab induction regimen.^1,2 This patient should complete his remaining 2 cycles of IV ipilimumab/nivolumab before being considered for the SC transition.

Best answer: (B) Resume IV nivolumab monotherapy first to monitor for hepatitis recurrence, then consider SC transition once stable.

Rationale: This patient experienced a severe immune-related adverse event (grade 3 hepatitis) during combination therapy. Per NCCN guidelines for ICI toxicity management, after a grade 3 hepatic irAE from a combination regimen, resumption of monotherapy anti-PD-1 may be considered once transaminases return to baseline and steroids have been tapered to ≤10 mg prednisone equivalent daily. However, approximately 1 in 3 patients may experience recurrence of the same irAE after rechallenge. Given this risk, it is prudent to resume IV nivolumab monotherapy initially so that the patient can be closely monitored during the first few cycles for any recurrence of hepatotoxicity. Once she has demonstrated tolerability over 2–3 cycles of IV nivolumab without hepatitis recurrence, transitioning to SC nivolumab would be reasonable. Switching directly to SC nivolumab during this vulnerable period, while not contraindicated per se, may provide less opportunity for the close monitoring warranted in this clinical situation.

Best answer: (A) Subcutaneous pembrolizumab is FDA-approved for adjuvant treatment following complete resection of stage IIB, IIC, or III melanoma, and patients receiving intravenous pembrolizumab may transition at their next scheduled dose.

Rationale: Keytruda Qlex, a fixed combination of pembrolizumab and berahyaluronidase alfa-pmph administered subcutaneously, is FDA-approved for the adjuvant treatment of adults and patients 12 years of age or older with completely resected stage IIB, IIC, or III melanoma. The prescribing information specifically states that patients receiving intravenous pembrolizumab may switch to Keytruda Qlex at their next scheduled dose; there is no requirement to complete a minimum number of intravenous treatment cycles before transitioning.^7,8

For an adult receiving pembrolizumab every 6 weeks, the corresponding subcutaneous regimen is Keytruda Qlex 790 mg pembrolizumab/9,600 units berahyaluronidase alfa-pmph every 6 weeks, administered over approximately 2 minutes by a healthcare professional. An every-3-week regimen of 395 mg/4,800 units administered over approximately 1 minute is also approved. In the adjuvant setting, treatment is continued until disease recurrence, unacceptable toxicity, or completion of up to 12 months.⁷

Importantly, changing formulations would not reduce the frequency of this patient’s treatment visits, because both her current intravenous regimen and the corresponding subcutaneous regimen are administered every 6 weeks. She would also continue to require clinical assessment, laboratory monitoring, and surveillance. Potential advantages of the subcutaneous formulation include avoiding intravenous access and reducing medication-administration time, but intravenous pembrolizumab remains an appropriate option. The choice should therefore reflect patient preference, comfort with the route of administration, institutional workflow, and treatment availability rather than an expectation of improved efficacy or fewer oncology visits.

This individualized approach is supported by the phase II MK-3475A-F11 crossover study, which included patients with resected stage IIB–III melanoma. Although 65% of evaluable participants preferred subcutaneous administration, primarily because of less time in the clinic, 32% preferred intravenous administration, most commonly because it felt more comfortable during administration.6 These findings emphasize that neither formulation is universally preferable.