Pharmacist’s Application to Practice
Retifanlimab-dlwr (Zynyz) for the treatment of adults with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC).
Corresponding FDA Drug Update:
Accelerated approval to retifanlimab-dlwr for metastatic or recurrent locally advanced Merkel cell carcinoma
What is the potential role for retifanlimab-dlwr in the treatment of metastatic or recurrent locally advanced MCC?
- Retifanlimab-dlwr is a humanized IgG4 monoclonal antibody against programmed cell death protein 1 (PD-1). Binding of the PD-1 ligand (PD-L1) expressed on tumor and immune cells in the microenvironment to the PD-1 receptor on T- cells inhibits T-cell activation and proliferation. PD-L1 is commonly expressed on MCC and blocking the PD-1:PD-L1 interaction with retifanlimab potentiates T-cell activity.1
- Approval for this indication was based on the POD1UM-201 trial, an open-label, multicenter, single-arm, phase II study in adults with metastatic or recurrent locally advanced MCC who had not received prior systemic therapy for their disease.2
- Patients (n=87) 18 years of age or older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, were treated with retifanlimab-dlwr 500 mg IV every 4 weeks for up to 2 years. The primary efficacy analysis was based on the first 65 patients assessed.
- The primary endpoint, overall response rate, as assessed by independent review per response evaluation criteria in solid tumors (RECIST) criteria was 46.2% (CR 12.3%). Median progression free survival was 13.8 months.
- 26.4% of patients had an immune-related adverse event (irAE) and 9.2% had a grade 3 or higher irAE.
- Retifanlimab-dlwr is listed in the National Comprehensive Cancer Network (NCCN) guidelines for MCC as an “other recommended regimen” for patients with recurrent regional disease (N+) or disseminated disease (M1) if patients are not amenable to surgery or radiation therapy. For disseminated disease (M1), other PD-1 inhibitors (avelumab, nivolumab, and pembrolizumab) are listed as preferred.3
- Response rates with retifanlimab-dlwr are relatively similar to other inhibitors of the PD1:PD-L1 pathway in this setting, including pembrolizumab (56% ORR), avelumab (40% ORR), and nivolumab (68%). Cross-trial comparisons of these single-arm studies are problematic given differences in patient characteristics, but a comparative trial between these agents has not been conducted (and may not be, given the relative rarity of diagnosis).4-7
- Biomarker studies (PD-L1 and viral status) are ongoing to determine patients most likely to respond to retifanlimab.
What role can the pharmacist play in the management of patients on retifanlimab-dlwr?1
- Pharmacists are crucial in the selection of therapies for patients and can select candidates for retifanlimab-dlwr therapy.
- The every 4 week treatment schedule may be an advantage of retifanlimab from a convenience point of view for patients.
- Pharmacists can help monitor for and manage irAEs with retifanlimab-dlwr.
- Patients should be counseled on irAEs, including but not limited to, pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic adverse effects. Patients should contact their healthcare provider immediately for any new or worsening signs or symptoms
- In general, retifanlimab should be held for severe (grade 3) irAEs and permanent discontinuation should be considered for life-threatening adverse reactions (grade 4).1
- Clinicians should refer to previously published guidelines regarding the management of irAEs in patients treated with immune checkpoint inhibitor therapy (e.g., ASCO guidelines).8
1.Retifanlimab-dlwr (Zynyz) [prescribing information]. Wilmington, DE: Incyte Corporation; 2023.
2.Grignani G, Rutkowski P, Lebbe C, et al. A phase 2 study of retifanlimab in patients with advanced or metastatic merkel cell carcinoma (MCC) (POD1UM-201). J ImmunoTher Cancer. 2021;9. doi: 10.1136/jitc-2021-SITC2021.545
3.National Comprehensive Cancer Network. Merkel Cell Carcinoma (Version 1.2023). https://www.nccn.org/professionals/physician_gls/pdf/mcc.pdf. Accessed June 30, 2023.
4.Nghiem PT, Bhatia S, Lipson EJ, et al. A. PD-1 blockade with pembrolizumab in advanced Merkel-cell carcinoma. N Engl J Med. 2016;374(26):2542-52.
5.D'Angelo SP, Lebbé C, Mortier L, et al. First-line avelumab in a cohort of 116 patients with metastatic Merkel cell carcinoma (JAVELIN Merkel 200): primary and biomarker analyses of a phase II study. J Immunother Cancer. 2021;9(7):e002646.
6.Topalian SL, Bhatia S, Hollebecque A, et al. Abstract CT074: Non-comparative, open-label, multiple cohort, phase 1/2 study to evaluate nivolumab (NIVO) in patients with virus-associated tumors (CheckMate 358): efficacy and safety in Merkel cell carcinoma (MCC). Cancer Res. 2017;77:CT074–4. doi: 10.1158/1538-7445.AM2017-CT074.
7.Tanda ET, d'Amato AL, Rossi G, et al. Merkel cell carcinoma: an immunotherapy fairy-tale? Front Oncol. 2021;11:739006.
8.Schneider BJ, Naidoo J, Santomasso BD, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update. J Clin Oncol. 2021;39(36):4073-4126.